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As whooping cough cases are surging globally, some may wonder if its necessary to get a booster.
Cases of the childhood respiratory disease also known as pertussis are surging internationally and in parts of the U.S., according to a recent report.
Bordetella pertussis is a type of bacteria that causes a very contagious respiratory infection that spreads from person to person through small respiratory droplets, per the CDC.
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"Reports indicate that whooping cough outbreaks are surging across Europe, Asia and parts of the United States, including Northern California, marking the largest uptick since 2012, with cases rising sharply since December," Maggie Rae, president of the Royal Society of Medicines epidemiological and public health section in London, told Fox News Digital.
Bordetella pertussis is a type of bacteria that causes a contagious respiratory infection that spreads from person to person through small respiratory droplets, per the CDC. (iStock)
In the U.K., there were an estimated 555 cases in January of this year and 913 cases in February compared to 858 cases for all of 2023, according to the UK Health Security Agency.
Cases in China totaled more than 15,000 this January. That's 15 times higher than the same time period last year, reports stated.
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"Concerns are mounting in Europe, especially in the Netherlands, where 1,800 cases were reported in the first two weeks of April, leading to four deaths, with declining childhood vaccination rates cited as a possible cause by public health officials," Rae said.
"This is a very important public health issue, and I would urge those members of the public who require a vaccine for pertussis to take this up."
Whooping cough is mostly controlled in the United States, although "breakthrough cases" can occur in people who are fully vaccinated.
Cases of the childhood respiratory disease known as whooping cough or pertussis are surging internationally and in parts of the U.S., according to a recent report. (iStock)
Clusters of cases in certain parts of the U.S. are expected for this time of year, according to the Centers for Disease Control and Prevention (CDC).
There have been small "clusters" of cases of whooping cough in the U.S., extending from San Francisco to New York City.
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A Catholic high school in San Francisco, California, has reported more than 12 cases since January, according to local reports.
The New York City Department of Health and Mental Hygiene estimated 244 cases from Oct. 1, 2023, to Jan. 31, 2024.
That's a 200% increase compared to the same time period in the prior year, a recent health advisory stated.
"This is a very important public health issue."
Most unvaccinated cases involved infants, while most vaccinated individuals were school-aged children.
A majority of adults had an unknown vaccination history, the advisory noted.
The U.S. typically has approximately 20,000 cases of pertussis per year. Yet as people donned masks and practiced physical distancing during the pandemic, annual cases dropped to 6,124 in 2020 and 2,116 in 2021, according to the CDC.
Clusters of cases often occur where there are large groups of young people, such as child care centers and schools.
"The symptoms of pertussis are initially like a cold, with a runny nose, and progress to a cough," Jennifer Duchon, M.D., hospital epidemiologist and director of antimicrobial stewardship at Mount Sinai Kravis Children's Hospital in New York, told Fox News Digital.
Patients tend to develop a cough that can become severe sometimes to the point of vomiting, Duchon said.
Health care providers typically test for the disease with a nasal swab. (iStock)
"The characteristic whooping sound is a gasp that is made when trying to breathe after a long episode of coughing," she added.
The cough can linger for weeks after a person catches pertussis.
When outbreaks occur, babies are at a high risk of getting sick and dying from the infection, health officials warn.
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"Pertussis is most severe in infants 6 months of age or less, especially in infants who were born preterm or are not immunized," Duchon said.
"Young infants can have a severe cough that impairs their ability to breathe, and can lead to episodes where they vomit, struggle to breathe or even cease breathing after bouts of coughing."
Patients tend to develop a cough that can become severe sometimes to the point of vomiting, a doctor said. "The characteristic whooping sound is a gasp that is made when trying to breathe after a long episode of coughing." (iStock)
Babies often wont make that whooping sound, so a warning sign is when their face turns blue as they struggle to breathe, the CDC noted.
The infection can progress to bacterial pneumonia or a condition called pulmonary hypertension, in which heart function is affected by the disease, Duchon warned.
Health care providers typically test for the disease with a nasal swab.
"If pertussis is caught early, patients can take an antibiotic called azithromycin, but this only helps make the disease less severe and does not cure the disease," Duchon noted.
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"If someone is exposed to pertussis and is at risk for severe disease or had a lot of contact with the ill person, doctors will sometimes recommend a short course of an antibiotic to act as a prophylaxis against the disease."
Currently, there are two kinds of vaccines for whooping cough available in the U.S., according to the CDC.
"The best way to prevent the disease is to make sure that all family members and health care workers are up-to-date on their vaccinations not only for pertussis, but also other vaccine-preventable diseases," Duchon told Fox News Digital.
"Children should get their primary series of vaccines at 2 months, 4 months and 6 months, and then at 15 months through 18 months, and at 4 years through 6 years," a doctor advised. (iStock)
The DTaP vaccine protects against diphtheria, tetanus and pertussis.
The Tdap vaccine protects against tetanus, diphtheria and pertussis.
The DTaP vaccine is for babies, while the Tdap "booster" vaccine is for pre-teens, teenagers and adults, per the CDC.
"Before vaccination became available, the disease used to be a major cause of mortality in young children," Duchon noted.
Due to the high risk to babies, the CDC recommends that pregnant women receive the Tdap vaccine during the 27th and 36th week of pregnancy, regardless of their prior vaccination status.
This prevents 78% of cases in infants younger than 2 months old and decreases hospitalization by 90% for infants younger than 2 months old who are infected with pertussis, according to the CDC.
"Everyone in close contact with a very young infant should be vaccinated against pertussis."
It is recommended that babies get immunized with the DTaP vaccine series, which provides immunity for three separate infectious diseases diphtheria, tetanus and pertussis.
"Children should get their primary series of vaccines at 2 months, 4 months and 6 months, and then at 15 months through 18 months, and at 4 years through 6 years," Duchon advised.
The Tdap vaccine protects against tetanus, diphtheria and pertussis. (iStock)
Adolescents should receive the Tdap vaccine at 11 to 12 years old to boost their immunity, the CDC recommends.
In children who receive the full series, 98% have full protection against the infection within a year after the last dose, but the response decreases to 71% after five years, the agency states.
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As pertussis immunity wanes from the original vaccination series in childhood, adults should get regular boosters, Monica Gandhi, M.D., professor of medicine and an infectious disease specialist at UCSF/ San Francisco General Hospital, told Fox News Digital.
"Although the exact frequency of the need for booster vaccination has not been precisely worked out, we recommend a tetanus vaccine every 10 years," she said.
The DTaP vaccine protects against diphtheria, tetanus and pertussis. (iStock)
As the pertussis vaccine comes formulated with tetanus immunization in the form of the Tdap vaccine, many practitioners recommend a pertussis vaccine every 10 years when the booster for tetanus is provided, according to Gandhi.
Other providers may only recommend routine pertussis boosters in certain circumstances, such as for pregnant women or adults who have never been vaccinated, Duchon added.
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"Everyone in close contact with a very young infant should be vaccinated against pertussis," she said.
"We call this strategy cocooning, where those around the baby form a protective wall against the disease."
For more Health articles, visit www.foxnews.com/health.
By Sam Tobin
LONDON (Reuters) - Pfizer and BioNTech asked a London court to revoke rival Moderna's patents over technology key to the development of vaccines for COVID-19, as the latest leg of a global legal battle began on Tuesday.
Pfizer and its German partner BioNTech sued Moderna at London's High Court in September 2022, seeking to revoke patents held by Moderna, which hit back days later alleging its patents had been infringed.
The competing lawsuits over the companies' two vaccines, which helped save millions of lives and made the companies billions of dollars, are just one strand of ongoing litigation around the world which focuses on messenger RNA (mRNA) technology.
Moderna says Pfizer and BioNTech copied mRNA advances it had pioneered and patented well before the COVID-19 pandemic began in late 2019.
U.S.-based Moderna is seeking damages for alleged infringement of its patents by Pfizer and BioNTech's Comirnaty shot on sales since March 2022.
Pfizer made $11.2 billion in sales from Comirnaty last year, while Moderna earned $6.7 billion from its vaccine Spikevax, illustrating the potentially huge sums at stake.
Pfizer and BioNTech, however, are asking the High Court to revoke Moderna's patents, arguing that Moderna's developments of mRNA technology were obvious improvements on previous work.
The London lawsuits have been split into three separate trials, with one due to consider Moderna's 2020 pledge not to enforce its vaccine-related patents during the pandemic starting next.
Pfizer, BioNTech and Moderna are also involved in parallel proceedings in Germany, the Netherlands, Belgium and the United States, much of which has been put on hold, as well as at the European Patent Office.
(Reporting by Sam Tobin; Editing by Sachin Ravikumar)
Representational image of a vaccine
The coronavirus was one tough cookie to beat. Much like the mythological Hydra, if you managed to kill one of its variants, it only came back with a stronger and meaner version, which often required an entirely new type of intervention (read: booster doses) to slay. Such is the fight against viruses in general, and why we still havent beaten the common cold, which has since mutated to 160 different strains now.
For this reason, coming up with a master vaccine that can eliminate all strains of the same family of viruses has seemed like a pipe dream ever since we started researching antivirals. However, scientists are pioneering a new vaccine platform that could do just that! And at the heart of this innovation lies one of the fundamental blocks of our cells: RNA.
For a refresher, RNAs are the intermediaries between the DNA and the protein-making process. Think of the DNA as a blueprint that tells you exactly how to make something, say, a house. The RNA copies the blueprint bit by bit and takes this message to centres with building materials, where the house can actually be constructed.
When a host is infected, their body produces small amounts of RNAs as an immune response to a viral infection. These fighters are called RNAis, and help kill the virus. To get around this setback, the viruses produce proteins that block the RNAi response.
The new technique attempts to manipulate the virus protein-manufacturing process in their new vaccine. Unlike traditional vaccines, which rely on the body's immune response, this method activates RNAi, offering a novel approach to viral defense.
The scientists found that if you weaken the virus first, it hinders their ability to block RNAi.
It (the virus) can replicate to some level, but then loses the battle to the host RNAi response. A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system, explains study author Shouwei Ding.
This new method even addresses the everlong mutation problem too. While traditional vaccines focus on deactivating a specific part of the virus to destroy them, the new RNAi method targets their whole genome, meaning that it will work for any future mutated strains as well. Or as the study authors put it, they cannot escape this.
Moreover, this platform presents a game-changer for vulnerable populations such as infants and individuals with compromised immune systems. By bypassing the need for traditional B and T cell immune responses, this vaccine holds promise for those typically ineligible for live vaccines.
Initial trials on mice, including genetically modified newborns devoid of B and T cells, have yielded promising results. A single injection provided robust protection against the Nodamura virus for an extended period, showcasing the platform's efficacy and potential longevity.
Looking ahead, the researchers aim to adapt this technology to tackle influenza, with plans for a nasal spray vaccine to alleviate needle-related concerns.
Our next step is to use this same concept to generate a flu vaccine, so infants can be protected. If we are successful, theyll no longer have to depend on their mothers antibodies, Ding notes.
While challenges remain, including extensive human trials and regulatory approvals, the prospect of universal protection against a spectrum of viruses looms tantalisingly close. With one shot, we could be looking to neutralise a multitude of human pathogens, including dengue, SARS and COVID.
The findings of this study have been published in Proceedings of the National Academy of Sciences and can be accessed here.
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Maine has reached herd immunity for school-required vaccination coverage for the first time since 2011, driven by a law that went into effect in 2021 that eliminated philosophical and religious exemptions for students attending K-12 schools.
Herd immunity is achieved when at least 95% of a population is immunized against infectious diseases.
Maine has become a leader in childhood vaccination, Dr. Puthiery Va, director of the Maine Center for Disease Control and Prevention, said in a statement Tuesday. It couldnt come at a better time, as the United States has already seen more measles cases in the first three months of 2024 than in all of 2023. This alarming trend highlights the importance of childhood vaccinations, which reduce the risk that Maines youngest residents could face from these harmful and potentially fatal diseases.
The U.S. CDC is reporting 125 cases of measles in 17 states (none in Maine) so far in 2024.
State lawmakers and the Mills administration prioritized improving Maines vaccination rates after years of high rates of religious and philosophical opt-outs left the state vulnerable to outbreaks of infectious diseases.
Lawmakers passed the bill in 2019, and it survived a peoples veto attempt that would have overturned the law before it was implemented. The new vaccine law went into effect in the 2021-22 school year.
Since then, as families have complied with the new requirements, vaccination coverage in schools has improved, plummeting from 4.5% opting out in 2020-21 the last year before the law was implemented to 0.8% in 2022-23 and 0.9% in 2023-24.
Medical exemptions are still permitted under the law, but religious and philosophic exemptions are no longer allowed.
Meanwhile, the percentage of students getting their first shots for diseases covered by school vaccination requirements including measles, mumps and rubella, pertussis, polio and others surpassed 95% for the first time since 2011, the Maine CDC said.
Herd immunity is the scientific term for when vaccination coverage among a population is so comprehensive that infectious diseases have few opportunities to gain a foothold. Public health experts say herd immunity is important in preventing highly contagious diseases from spreading in populations.
Achieving herd immunity among schoolchildren represents a pivotal success for Maine, Jeanne Lambrew, commissioner of the Maine Department of Health and Human Services, said in a statement.
The percentage of students immunized against specific diseases can differ from the overall vaccination rate for several reasons, primarily because of missing vaccination records. Even if a parent has their child vaccinated, the child will be listed as unvaccinated if the school doesnt have the vaccination record to turn over to the state CDC.
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Synthesis of the PNAG oligosaccharide library
To date, only fully acetylated and fully deacetylated PNAG oligosaccharides have been investigated as immunogens for vaccine studies13,14,15. The availability of a library of PNAG oligosaccharides with systematically varied numbers and locations of free amines can greatly aid in the identification of the maximally protective epitope structures. We aimed to synthesize a comprehensive library of 32 pentasaccharides designated PNAG0PNAG31 (Fig.1) fully covering the free amine space of PNAG. The reducing ends of the target pentasaccharides bear a linker terminated with a disulfide group, which can be reduced for chemoselective conjugation to a carrier protein.
The five-digit number in the bracket for each compound codes for free amine (0) or N-acetamide (1) at residues ABCDE from the non-reducing end to the reducing end of the pentasaccharide, respectively. The five-digit number was then viewed as a binary number and converted to the decimal system as the compound number. For example, 01010 in binary number is equivalent to 10 in the decimal system. Thus, the PNAG pentasaccharide bearing N-acetylation at units B and D only is named as PNAG10.
While several PNAG structures have been synthesized before16,17,18,19,20, a general method for the expeditious construction of a comprehensive PNAG pentasaccharide library is lacking. To accelerate the library synthesis, rather than starting from monosaccharide building blocks for each targeted pentasaccharide, we envisioned the overall efficiency can be significantly enhanced with a divergent strategy. In our synthetic design, the amine groups of strategically protected pentasaccharides are differentiated by orthogonal protective groups for selective deprotection and acetylation. After screening multiple synthetic intermediates, we developed two key linchpin pentasaccharide intermediates (1 and 2), which bear four protective groups, i.e., tert-butyloxycarbonyl (Boc), allyloxycarbonyl (Alloc), 2,2,2-trichloroethoxycarbonyl (Troc), and fluorenylmethoxycarbonyl (Fmoc), on glucosamine units A, B, C, and D. The reducing end glucosamine unit E is N-acetylated (for compound 1) or N-trifluoroacetylated (for compound 2) (Fig.2A).
A Structures of two key linchpin pentasaccharide intermediates (1 and 2). B Synthesis of the reducing end glucosamine building block 8. C Syntheses of compound 13; D Syntheses of compound 1. Ac acetyl, Alloc allyloxycarbonyl, Bz benzoyl, TBDPS tert-butyldiphenylsilyl, Boc tert-butyloxycarbonyl, DIPEA diisopropylethylamine, Fmoc fluorenylmethoxycarbonyl, HATU hexafluorophosphate azabenzotriazole tetramethyl uronium, and Troc 2,2,2-trichloroethoxycarbonyl.
Based on the above design, our synthesis commenced from thioglycoside 3, which glycosylated 3-azido-1-propanol 4 to provide compound 5 in 82% yield (Fig.2B). Upon removal of the Alloc group from 5 and N-acetylation, the resulting compound 6 was subjected to azide reduction, amidation of the free amine with carboxylic acid 7, and protective group adjustments leading to compound 8 in 45% yield for the four steps.
Oligosaccharide assembly started from the CD disaccharide 9 containing N-Troc and N-Alloc groups (Fig.2C). Thioglycoside donor 10 was preactivated with the p-TolSCl/AgOTf promoter system21 at 78C. Upon complete activation, the thioglycosyl acceptor 11 was added to the reaction mixture leading to disaccharide 9 in 83% yield (Fig.2C). In order to extend the glycan chain, the glycosylation of acceptor 8 with disaccharide 9 was performed. When the reaction was first carried out under the pre-mix condition, i.e., 9 and 8 were mixed together followed by the addition of promoter (p-TolSCl/AgOTf or NIS/TfOH22,23), little desired trisaccharide 12 was obtained, which was likely due to the activation of the thioester moiety by the thiophilic promoter. Next, the reaction was explored under the pre-activation condition by activating 9 with the promoter p-TolSCl/AgOTf first, followed by the subsequent addition of acceptor 8. This change of the reaction protocol successfully produced trisaccharide 12 in 71% yield. Replacement of Alloc with Fmoc and removal of TBDPS group from 12 resulted in the trisaccharide 13. To extend 13 to a pentasaccharide, the Troc moiety of disaccharide 9 was replaced with Boc (disaccharide 14, Fig.2D). Pre-activation-based glycosylation of 14 and 13 produced pentasaccharide 1, which contains four different N-protective groups on units A, B, C, and D. Analogously, pentasaccharide 2 was synthesized with four different N-protective groups on units A, B, C, and D, and the N-TFA group on unit E (Supplementary Fig.1).
With the two key pentasaccharides in hand, we explored orthogonal deprotection of pentasaccharides 1 and 2. As an example, the Boc and Alloc groups of compound 2 could be removed by 90% aqueous TFA and Pd(PPh3)4/PhSiH3, while deprotections of Troc and Fmoc were accomplished using Zn/AcOH and 20% piperidine in N,N-dimethylformamide (DMF), respectively, without affecting any other amine protective groups (Fig.3A). These results suggest that the four amine protective groups could be independently removed specifically.
A Orthogonal deprotection of pentasaccharide 2. B Divergent syntheses of 16 PNAG pentasaccharides from the strategically protected pentasaccharide 1. C Divergent syntheses of 16 PNAG pentasaccharides from the strategically protected pentasaccharide 2. Ac acetyl, Alloc allyloxycarbonyl, Bz benzoyl, TBDPS tert-butyldiphenylsilyl, Boc tert-butyloxycarbonyl, DIPEA diisopropylethylamine, DMF dimethylformamide, Fmoc fluorenylmethoxycarbonyl, HATU hexafluorophosphate azabenzotriazole tetramethyl uronium, Troc 2,2,2-trichloroethoxycarbonyl, and TFA trifluoroacetic acid.
With the orthogonal deprotection conditions established, divergent modifications of the key pentasaccharide intermediates were carried out. Treatment of pentasaccharide 1 with 90% TFA cleaved both Boc and TBDPS groups (Fig.3B). Upon acetylation of the newly liberated hydroxyl and amine moieties, the Alloc, Troc, and Fmoc groups were subsequently removed followed by full O- and S-deacylation with 20% hydrazine hydrate in MeOH, affording PNAG17 pentasaccharide in 48% overall yield bearing the N-acetylglucosamine (GlcNAc)-glucosamine (GlcN)-GlcN-GlcN-GlcNAc (10001) sequence. Alternatively, following TFA treatment of 1, the Fmoc group was cleaved, which was then acetylated with subsequent removal of Troc, Alloc, and Bz moieties to produce pentasaccharide PNAG19 with the GlcNAc-GlcN-GlcN-GlcNAc-GlcNAc sequence (10011) in 51% overall yield. Similar divergent modification processes on the two key pentasaccharides 1 and 2 produced the full library of 32 PNAG pentasaccharides with all possible combinations of free amines in each glucosamine unit of the pentasaccharides (Fig.3B, C).
As carbohydrate antigens in general are T cell independent B cell antigens24 and small oligosaccharides alone are not immunogenic25, these types of antigens need to be conjugated to an immunogenic carrier in order to induce anti-carbohydrate IgG antibody responses. The mutant bacteriophage Q (mQ)26 is a powerful carrier and likely highly useful for carbohydrate based conjugate vaccines27,28,29. As PNAG oligosaccharides can potentially contain multiple free amine moieties, we resorted to sulfhydryl chemistry for PNAG/mQ conjugation. The mQ A38K/A40C/D102C was expressed in E. coli, purified, and incubated with the bifunctional linker succinimidyl 3-(bromoacetamido)propionate (SBAP) 19 to react with free amines on the mQ surface (Fig.4A). Upon removal of the excess linker, the SBAP functionalized mQ was added to the PNAG pentasaccharide followed by quenching the unreacted bromoacetamide moieties on mQ with cysteine to avoid any potential side reactions of residual bromoacetamide on mQ upon storage or following vaccination. MALDI-TOF mass spectrometry (MS) analysis of the mQPNAG conjugate showed an average loading of 250 copies of pentasaccharide per particle (Supplementary Fig.2A). It is known that the antigen loading density on Q can significantly impact the levels of antibodies induced against the target antigen29,30. When the loading level of antigen was low (<50 copies per particle), despite the same total amount of antigen administered, the antibody responses induced were low29,30. Increasing the local density of the antigen on the particle (over 100 antigens per particle) can significantly improve the antibody responses, which is presumably due to the more effective crosslinking of the B cell receptors on B cells31. The loading density of PNAG on the mQPNAG conjugate was higher than the threshold antigen level needed for powerful B cell activation.
Syntheses of A mQPNAG, B TTHcPNAG, and C BSAPNAG conjugates. SBAP succinimidyl 3-(bromoacetamido)propionate, TCEP tris(2-carboxyethyl)phosphine, TThc tetanus toxoid heavy chain.
With the mQPNAG conjugates in hand, their abilities to induce anti-PNAG antibodies were evaluated. The conjugate of TT with the PNAG pentasaccharide bearing five free amines (5GlcNH2TT) has undergone a phase 1 human clinical trial32. To compare with our mQPNAG conjugate, we covalently linked PNAG0 (5GlcNH2) with the TT heavy chain (TTHc) using SBAP and achieved an average loading of 4.7 PNAG0 per protein molecule (Fig.4B and Supplementary Fig.2B). The recombinant TTHc is a suitable surrogate of TT33. As the molecular weight of mQ particle (2540kDa for the protein shell) is about 49 times that of the TTHc (MW~52kDa), the overall densities of PNAG0 on mQPNAG0 and TTHcPNAG0 were similar.
Head-to-head comparative immunogenicity studies of the mQPNAG0 and the TTHcPNAG0 conjugates were carried out. Groups of female C57Bl6 mice (n=5 per group) were immunized with freshly prepared mQPNAG0 (8nmol corresponding to 8g of PNAG0 per injection) or the TTHcPNAG0 conjugate (8nmol PNAG0 per injection) on days 0, 14, and 28. Monophosphoryl lipid A (MPLA, 20g) was added to each vaccination as the adjuvant. A control group of mice received a mixture of mQ with PNAG0 at equivalent total amounts of mQ, PNAG0, and MPLA following the same immunization protocol. On day 35, sera were collected from all mice.
To analyze the levels of antibodies generated, enzyme linked immunosorbent assay (ELISA) analyses were performed. To avoid the interference of anti-mQ antibodies in the sera, the 32 PNAG pentasaccharides were conjugated with BSA individually (Fig.4C and Supplementary Fig.3) and used as the ELISA coating antigens. As shown in Fig.5A, mQPNAG0 induced high anti-PNAG IgG titers (EC50 IgG titers GMT 75,613, measured against BSAPNAG0) while the IgM titers were negligible (GMT<1000). Furthermore, high levels of anti-PNAG0 IgG responses were observed more than 1 year after the initial immunization (Fig.5B). The IgG levels could be boosted back to near peak levels after nearly 2 years indicating that the mQ conjugate induced PNAG0 specific memory B cells through immunization. The GMT of 75,613 achieved in mice receiving the mQPNAG0 was significantly (P<0.0001, Dunnetts multiple comparisons test) higher than the anti-PNAG0 IgG titers achieved in mice immunized with the corresponding TTHcPNAG0 conjugate (GMT 4765), highlighting the superior immunogenicity of the mQ carrier for conjugate vaccines. Mice immunized with the admixture of mQ and PNAG0 did not produce any detectable levels of anti-PNAG0 IgG (GMT<1000), accentuating the critical need to covalently conjugate mQ with PNAG0.
A C57Bl6 mouse (n=5 per group) antibody responses at day 35 after immunization. The EC50 value (the fold of serum dilution that gives half-maximal binding) of the IgG titers to the immunizing oligosaccharide was plotted with each symbol representing one animal and the horizontal line is the geometric mean value of the titers within the group. The ELISA titers were determined using the BSAPNAG conjugate containing the same PNAG structure as the immunizing QPNAG construct. One-way ANOVA allowed for rejection of the null hypothesis that all groups have the same mean IgG titers (P<0.0001). Statistical significance was performed by Dunnetts multiple comparisons post-hoc test. ****P<0.0001; B Anti-PNAG0 IgG antibody responses of mice (n=5) immunized with mQPNAG0 monitored over time with mean titers plotted. Data are presented as mean valuesstandard deviation of the titer numbers from five mice. The arrows indicate days of vaccination (days 0, 14, 28, 360, and 655). The antibody responses could be boosted more than 650 days after prime vaccination. Source data are provided as a Source Data file.
As C57Bl6 mice are inbred, to enhance the rigor of our study, we immunized outbred CD1 mice with the mQPNAG0 conjugate following the same immunization protocol. mQPNAG0 was able to elicit comparably high titers of anti-PNAG0 IgG antibodies on day 35 after the primary series of immunization in CD1 mice (Supplementary Fig.4).
The precise PNAG sequences synthesized by pathogens such as S. aureus are not known. Furthermore, the most abundant PNAG structure on cell surfaces that would encompass a highly (8095%) acetylated polysaccharide is not a protective epitope13. To guide vaccine design, we envisioned anti-PNAG mAb F598 could provide valuable information regarding optimal acetylation patterns in a PNAG pentasaccharide. Isolated from a patient who recovered from an S. aureus infection, mAb F598 can protect mice against S. aureus infections34. The 32 PNAG pentasaccharideBSA conjugates were immobilized onto a glycan microarray35. Following incubation of mAb F598 with the microarray and washing, the amount of antibody remaining bound was quantified with a fluorescent secondary antibody. Interestingly, although mAb F598 was initially identified due to binding to deacetylated PNAG with only ~15% N-acetylation34, it had little binding to glycan PNAG0 or any glycans containing only one Ac moiety. Highly acetylated PNAG such as PNAG30 and PNAG31 with four or more consecutive GlcNAcs were among the strongest binders (Fig.6). Both the location and the number of NHAc are important for F598 binding, supporting the idea of an amine/acetylation code. For example, despite having the same total number of NHAcs (4 in the molecules), PNAG23 (10111) is a weak binder with an apparent affinity <5% of that with PNAG30 (11110). Out of the PNAGs with two or three GlcNAc residues, PNAG10 and PNAG26 were the strongest binders, respectively.
A Relative fluorescence unit (RFU) of F598 mAb binding with the library of 32 PNAG pentasaccharides. The glycans are grouped according to the number of NHAc units in the molecule. Each PNAG sequence is printed five times on the glycan microarray. The error bars represent the standard deviations of five individual spots. Data are presented as mean valuesstandard deviation. F598 generally prefers highly acetylated PNAG sequences. Both the location and the number of NHAc units are important determinants of F598 binding. B Quantification of the preference of F598 for acetylation at each site of the PNAG pentasaccharide. The mean values are calculated from the values of the binding intensities of all 32 PNAG sequences to F598. Each PNAG sequence is printed five times on the glycan microarray. Data are presented as mean valuesstandard deviation. Source data are provided as a Source Data file.
To better interpret the binding data, we quantified the GlcNAc binding preference of F598 by computing the preference index (P) for each unit of the pentasaccharide as
$${P}_{i}=frac{mathop{sum}limits_{j}{R}_{j}times {A}_{i}}{mathop{sum}limits_{j}{R}_{j}}$$
(1)
where (i) (AE) is the site of monosaccharide from the non-reducing end to the reducing end, (j) (031) is the serial number of glycan, (R) is the intensity of the binding signal (RLU), and (A) is the code for amine vs acetylation (A=1 for free amine and A=1 for NHAc). P value indicates the conditional probability difference between finding an NHAc or free amine for binding, which ranges from 1 to 1 with 1 and 1 indicating a complete preference for free amine or NHAc, respectively, at the specific site. As shown in Fig.6B, unit B position showed the highest P value of 0.91, suggesting on average that there is a 95.5% chance to find an NHAc moiety rather than a free amine on saccharide B for ligand binding with F598. The P values for sites A, C, and E were between 0.31 and 0.54 indictive of a moderate global preference for N-acetylation. There were almost no preferences for NHAc or free amine for site 5 as the P value at this site was close to 0.
The importance of an NHAc at unit B identified from microarray binding can be rationalized by the crystal structure of F598 complexed with fully acetylated PNAG oligosaccharides (PDB 6be4)36. The binding pocket of F598 could accommodate PNAG with five GlcNAc residues. The NHAc groups on saccharides B and D in the binding pocket were deeply inserted into the groove clamped by the heavy and the light chain of the mAb, forming multiple hydrogen bonds, while the NHAcs on units A, C, and E only had weak to moderate interactions with the antibody. The carbonyl oxygen of the NHAc on saccharide B forms a hydrogen bonding with light chain A32 backbone amide while bridging with light chain R52 residue via a water molecule. The carbonyl oxygen of NHAc on saccharide D also formed hydrogen bonds with light chain A97 backbone amide and the hydroxyl of heavy chain Y50. Those interactions supported the relatively high dependence of NHAc on sites B and D for the binding of F598.
Based on the microarray results and the report that antibodies raised against the fully acetylated PNAG antigen were poorly protective13,14,15, we selected PNAG10 and PNAG26 as new PNAG oligosaccharide antigens for further evaluations. PNAG10 has the strongest binding to F598 among all PNAG structures with two or fewer NHAcs, and PNAG26 is the best binder among all structures with three or fewer NHAcs. Both PNAG10 and PNAG26 have NHAcs on glycan sites B and D. PNAG0 was utilized as a positive control since the corresponding TTPNAG0 construct (5GlcNH2TT) has entered clinical trials [ClinicalTrials.gov Identifier: NCT02853617].
C57/Bl6 mice were immunized with the mQ conjugates of PNAG10 or PNAG26 following the aforementioned immunization protocol (8nmol PNAG, three injections on days 0, 14, and 28 with MPLA adjuvant). ELISA analysis of the immune sera showed significantly enhanced IgG antibody titers against the immunizing antigen (PNAG10 or PNAG26) with GMTs of 191,141 and 227,064 ELISA units, respectively, as compared to pre-immune sera (Fig.5A). Similarly, mQPNAG10 or PNAG26 conjugates induced high levels of anti-PNAG10 and anti-PNAG26 IgG antibodies, respectively, in CD1 mice (Supplementary Fig.4).
To demonstrate the immunogenicity of the mQ conjugates in an additional mammalian species, New Zealand white rabbits were immunized with mQ conjugates of PNAG0, PNAG10, and PNAG26 (8nmol PNAG per injection) following a similar prime-boost protocol as that used in the mouse study. ELISA analysis of the post-immune sera showed that all three constructs induced strong anti-PNAG IgG responses with EC50 titers over 100,000 ELISA units (Fig.7A), while those for the pre-immune sera were below 1000 ELISA units. No side effects due to vaccinations were observed in either rabbits or mice.
A IgG antibody titers to the immunizing PNAG oligosaccharide in rabbit (n=2 per group) sera on day 35 after prime vaccination. B IgG antibody titers in pooled rabbit sera from mQ-conjugate or 5GlcNH2TT conjugate immunized animals (n=2 per group) as well as titer of natural human IgG in pooled human serum against native PNAG polysaccharide purified from Acinetobacter baumannii. The numbers above symbols are the average titer numbers. Titers and 95% confidence intervals (CI) were determined by linear regression using log10 values of the average of replicate serum dilutions to determine the X intercept and 95% CI when Y=0.5 (OD405nm of ELISA plate reading). C Stacked bar graphs depicting the IgG signals at the serum dilution of 1:50,000 for each rabbit (n=2) immunized with mQPNAG0, mQPNAG10, and mQPNAG26 as well as pre-immune sera, respectively, on the array. The complete microarray results are provided in the Source Data file; D Normalized binding of the comprehensive library of PNAG pentasaccharides by IgG antibodies from post-immune sera of rabbits immunized with mQPNAG0, mQPNAG10, and mQPNAG26, respectively, as well as pre-immune sera. PNAG sequences are grouped together according to the total number of acetamides in the molecules. The color scale bar is shown on the right with 100% indicating the strongest binding to a PNAG component and 0% indicating the weakest binder. For each antigen, the two rows represent sera from two rabbits per group immunized with the specific construct. Source data are provided as a Source Data file.
We analyzed next the recognition of native PNAG using PNAG polysaccharide isolated from Acinetobacter baumannii37,38 as the coating antigen for ELISA. As shown in Fig.7B, control sera from rabbits immunized only with the Q carrier did not bind with PNAG. In contrast, sera from rabbits immunized with mQPNAG0, mQPNAG10, and mQPNAG26 exhibited strong binding with mQPNAG26 antiserum having the highest titer (1,584,983 ELISA units) to the native microbial polysaccharide. As a comparison, sera from the conjugate of 5GlcNH2TT13,15 immunized rabbit only gave a titer of 501 ELISA units (Fig.7B). Normal human sera containing natural antibodies to PNAG had an average ELISA titer of 631 ELISA units. These results further highlight the potential of mQPNAG conjugates as vaccines.
Analysis of the microarray binding by post-immune sera revealed selective PNAG epitope recognition by the post-immune sera (Fig.7D). Rabbits immunized with mQPNAG0 produced serum IgG antibodies exhibiting the strongest binding with the immunizing PNAG0 antigenic structure. Other good binders include PNAG1 and PNAG8, both having a single GlcNAc in the structure. Interestingly, for PNAG4 with the sequence of GlcN-GlcN-GlcNAc-GlcN-GlcN, although it also only contains one GlcNAc, it had much lower binding with the sera (about 30% that to PNAG1). This suggests that three or more consecutive GlcNs are important for binding by anti-PNAG0 sera.
mQPNAG10 immunized rabbits produced serum antibodies that preferentially bind to PNAG8 (01000) and PNAG10 (01010), which differ only by the GlcNAc in residue D indicating the non-reducing end GlcN-GlcNAc-GlcN may be the main epitope. Serum antibodies from mQPNAG26 (11010) immunized rabbits preferentially bound to PNAG25 (11001), PNAG26 (11010), PNAG8 (01000), and PNAG16 (10000) suggesting GlcNAc-GlcNAc-GlcN and GlcNAc-GlcN-GlcN may be part of the epitopes being recognized.
For an effective vaccine, it is important to establish that the post-immune sera bind not only the isolated antigen but also the antigen expressed on pathogen cells. We reacted S. aureus ATCC29213 cells with rabbit immune sera and the bound antibodies were detected by a fluorescently labeled anti-rabbit IgG secondary antibody. As shown in Supplementary Fig.5A, fluorescence microscopy images showed stronger binding to bacterial cells by IgG antibodies in mQPNAG10 and mQPNAG26 immune sera compared to sera from mQPNAG0 immunized rabbits or pre-immune sera. To validate pathogen recognition observed in fluorescence images, whole cell ELISA was performed. S. aureus cells were coated on ELISA plates, incubated with rabbit immune sera, and detected by secondary antibodies. The post-immune sera exhibited significantly higher titers in binding with the cells compared to pre-immune sera (Supplementary Fig.6).
For antibody-mediated complement deposition39, we added various immune sera to wells coated with purified PNAG isolated from Acinetobacter baumannii37,38 along with IgG/IgM depleted 2.5% human complement (Fig.8A). After incubation, the immobilized complement component C1q was detected by anti-C1q antibodies. As shown in Fig.8A, sera from mQPNAG10 and mQPNAG26 deposited significantly more C1q than those from mQPNAG0 immunized rabbits, which in turn had more potent C1q binding than antibodies in sera from rabbits immunized with the 5GlcNH2TT conjugate13,15.
A Complement deposition tests were performed as described39 using pooled sera from rabbits (n=2 per group) immunized with mQPNAG conjugates, the 5GlcNH2TT conjugate, or from a sample of pooled normal human sera. Titers and 95% confidence intervals (CI) were determined by linear regression using log10 values of the average of replicate serum dilutions to determine the X intercept and 95% CI when Y=0.5 (OD405nm of ELISA plate reading). P values indicate the significance of the deviation of the slope of the titration curve from zero to identify sera with activity at P<0.05. mQPNAG10 and mQPNAG26 conjugates were more potent than the mQPNAG0 and 5GlcNH2TT conjugate in inducing C1q deposition onto purified PNAG. Normal human serum had no significant C1q depositing activity in spite of having a binding titer to PNAG (see Fig.7B) consistent with prior reports that naturally acquired human antibody to PNAG is not functional due to the inability to activate the complement pathway12,34. Titers were determined by simple linear regression. B Pooled sera from rabbits (n=2 per group) immunized with mQPNAG conjugate led to significantly higher levels of opsonic killing activities against S. aureus cells. Three aliquots were prepared from each pooled serum and the individual values of the three aliquots were presented. Source data are provided as a Source Data file.
The abilities of the post-immune sera to kill bacteria in vitro were evaluated next via the opsonophagocytic killing (OPK) assay. S. aureus cells were treated with pooled rabbit immune sera, followed by the addition of complement/phagocytic cells and quantification of the number of bacterial cells surviving the opsonic killing. As shown in Fig.8B, while the pre-immune sera were completely ineffective, all three constructs induced antibodies with potent in vitro killing activity. mQPNAG26 (EC50: 2534) and mQPNAG10 (EC50: 3045) showed higher EC50 OPK titers as compared to mQPNAG0 (EC50: 1345). Omitting either immune sera, complement or phagocytic cells resulted in complete loss of killing activity (Supplementary Fig.7), indicating the need for all three components for protective immunity.
The efficacy of the various vaccine constructs in protecting against bacterial infection was tested in two mouse bacteremia challenge models. According to the CDC, bloodstream infections by S. aureus are serious threats with nearly 20,000 deaths per year in the USA4. For the in vitro study, we first compared the mQPNAG0 vs TTHcPNAG0 construct. In the active protection model, mice were immunized three times with mQPNAG0 or TTHcPNAG0 at equivalent doses (8nmol PNAG0) (n=20 for each group) (Fig.9). Another group of control mice received a mock injection of saline. Two weeks following the last vaccination, each mouse was challenged via the tail vein with 10*LD50 of the S. aureus strain ATCC29213. Mice that had received saline all died within 2 days of bacterial challenge. On the other hand, 95% of the mice receiving mQPNAG0 were protected against death from this pathogen. The survival rate of the mQ vaccine group was significantly better than TTHcPNAG0 vaccinated group (p=0.0154, logrank test) (Fig.9A). Bacteria were detected in the kidneys of 35% (7 out of 20) of the mice immunized with TTPNAG0, while mQPNAG0 vaccination reduced the recovered levels of S. aureus from the kidneys with bacteria only observed in 5% of the mice (1 out of 20) (Fig.9B). Contingency table analysis of the proportion of the 20 immunized mice in each group with or without detectable S. aureus by Fishers exact test showed significantly (p=0.0436) fewer infected kidneys in the mQPNAG0 immunized group, with a relative risk of 0.68 (95% CI=0.450.93). Thus, disease burden evaluated by the levels of S. aureus in mouse kidneys was significantly better in mQPNAG0 vaccinated group compared to those receiving the TTHcPNAG0 vaccine. These results further support the superior performance of the mQ carrier.
Immunization with mQPNAG0 effectively A protected against S. aureus infection, and B reduced bacterial count in mouse kidney. mQPNAG0 was significantly better than TTHcPNAG0 in protecting mice and reducing disease burden (n=20 for each group). Logrank tests were performed for statistical analysis. P values were presented in the graph. ****P<0.0001. Source data are provided as a Source Data file.
As the mQPNAG0 immunogen gave almost complete protection in the active protection model in mice, we next established a passive protection model to differentiate the various mQPNAG constructs, using rabbit sera transferred to mice. The passive model can be a more stringent test by using more dilute sera for protection. Rabbit sera were diluted 800-fold and administered intraperitoneally to mice, which were then challenged with 10*LD50 (200 million cells) of S. aureus ATCC29213 via the tail vein (Fig.10). While all control mice receiving the pre-immune sera died within 3 days of this challenge, all post-immune sera from PNAG0, PNAG10, or PNAG26 immunized rabbits bestowed significant protection.
Transfer of antisera from mQPNAG immunized rabbits to mice A provided significant protection to mice (n=10 per group) against the lethal challenges by S. aureus ATCC29213. Statistical analysis was performed with the logrank test. ****P<0.0001; and B significantly reduced bacterial count in mouse kidneys. The combination of sera from mQPNAG0 and mQPNAG26 immunized rabbits provided complete protection to mice. Statistical analysis for survival was performed using the logrank test. Analysis of S. aureus cfu/gm was by KruskalWallis non-parametric ANOVA (P<0.0001 for overall effect of serum given). P values for pairwise comparisons are shown on graph by Dunns multiple comparisons test. Transfer of antisera from mQPNAG immunized rabbits to mice C provided significant protection to mice against the lethal challenges by MRSA strain 1058 (n=10 per group); statistical analysis for survival was performed using the logrank test; and D reduced bacterial count in mouse kidneys. Sera from mQPNAG26 immunized rabbits provided the highest protection to mice. The horizontal line represents the median value of each group. Statistical analysis for survival was performed using the logrank test. Analysis of MRSA cfu/gm was by KruskalWallis non-parametric ANOVA (P=0.0967). P values for pairwise comparisons are shown on graph by Dunns multiple comparisons test. Source data are provided as a Source Data file.
Mice receiving sera from mQPNAG26 and mQPNAG10 immunized rabbits showed higher survival rates than those receiving PNAG0 sera (Fig.10A) (60% and 50%, respectively, vs 30%) and lower pathogen load compared to mQPNAG0 sera supporting the in vitro opsonic killing data (Fig.10B). We next tested the combination of two sera. Interestingly, administering the mixed PNAG26 and PNAG0 sera (1:1 ratio with each individual serum diluted 1600 times, which is regarded equivalent in concentration to 1:800 dilution of a single serum) provided 100% protection to mice against the 10*LD50 challenges with S. aureus (Fig.10A). The kidneys of mice receiving the combination of PNAG26 and PNAG0 sera had no detectable bacteria (Fig.10B). The higher protective efficacy observed with the combined sera was presumably because the PNAG polysaccharide can be heterogenous in the amine/acetylation patterns. While some of the sequences such as the fully deacetylated PNAG0 may be rare within the native PNAG polysaccharide, antibodies generated by mQPNAG0 can complement those by mQPNAG26. Thus, the combination of two mQPNAG constructs can broaden bacterial recognition and enhance protection against bacterial challenges.
The emergence of MRSA is a pressing public health concern40. Effective vaccines can provide a complementary tool to combat S. aureus infections and reduce the reliance on antibiotics. The post-immune rabbit sera were tested against multiple MRSA strains including six clinical strains first via immunofluorescent staining (Supplementary Fig.5B and Supplementary Table1). All three mQPNAG sera recognized the seven strains tested highlighting the breadth of immune recognition. A control strain lacking PNAG expression with icaA gene knock out (954) showed negligible binding by the immune sera, indicating the recognition is PNAG dependent. Next, rabbit sera were diluted 800 times and administered to mice, which were then challenged with 10*LD50 (200 million cells) of the MRSA strain 1058 via the tail vein (Fig.10C). Sera from mQPNAG26 immunized rabbits protected 90% of the mice from MRSA-induced death, which was significantly higher than the 40% protection by mQPNAG0 sera. Correspondingly, mice receiving mQPNAG26 rabbit sera had the lowest overall bacterial load in the kidneys of challenged mice (Fig.10D).
As PNAG is expressed in many types of bacteria, we explored the effects of immunization on gut microbiome. To analyze the composition of the gut microbiome, mice were fully immunized with mQPNAG26, and feces were collected on day 0 prior to immunization and day 35 following the initial prime immunization. The microbial species present in the droppings were analyzed via the 16S rRNA sequencing. Despite the significant amounts of anti-PNAG IgG produced in mouse sera, there were no significant changes in the microbial community present in the mouse gut (Supplementary Fig.8). Similar results were reported in a sponsored trial of the 5GlcNH2TT vaccine and shown in the study of anti-PNAG therapy in the setting of graft-versus-host disease41, or in human subjects in phase 1 clinical trials of both the 5GlcNH2TT vaccine or anti-PNAG mAb42,43. These observations corroborate that immunity to PNAG does not significantly alter the gut microbiome in immunized animals highlighting the potential safety of the vaccine.
In summary, numerous pathogens produce PNAG, rendering it a highly attractive target for vaccine development with the conjugate of fully deacetylated PNAG pentasaccharide with TT carrier currently undergoing human clinical trials as an anti-microbial vaccine. In order to enhance the potential protective efficacy, several aspects of the PNAG-based vaccine can be improved. As carbohydrates are typically T cell independent B cell antigens, an immunogenic carrier is critical. We have demonstrated that mQ is a powerful carrier. The mQPNAG conjugate was found to be superior in inducing higher levels of anti-PNAG IgG antibodies as compared to the corresponding PNAG conjugate with the TTHc carrier.
Besides the carrier, another important factor in vaccine design is the identification of the protective epitope(s) of the PNAG antigen, which was hampered by the lack of diverse structurally well-defined PNAG compounds. To gain a deeper understanding of the epitope specificity, a comprehensive library of PNAG pentasaccharides covering all possible combinations of free amine and NHAc has been synthesized. The synthesis is highlighted by a divergent design through the judicious choice of four amine protective groups, which can be orthogonally removed without affecting each other. The library of 32 PNAG pentasaccharides was obtained from just two strategically protected pentasaccharide intermediates, thus significantly enhancing the overall synthetic efficiency.
The availability of the comprehensive library provided an exciting opportunity to probe the epitope specificity through a glycan microarray. Screening of an anti-PNAG mAb F598 on the microarray suggests that the NHAc at unit B plays a critical role in F598 binding. NHAc at unit D could further enhance the binding. This knowledge led to the addition of two PNAG sequences (PNAG10 and PNAG26) beyond the fully deacetylated PNAG0 for vaccine studies.
The mQ conjugates with PNAG10 and PNAG26 were found to elicit IgG antibodies capable of inducing high levels of complement deposition and opsonic killing of bacteria compared to the mQPNAG0 conjugate. Vaccination with mQPNAG conjugate provided effective protection to mice against lethal challenges by S. aureus in both active and passive immunity models. Mice were also effectively protected from MRSA-induced death by the immune sera with significantly reduced bacterial load in the kidneys. The vaccines are biocompatible with no adverse side effects and do not significantly disturb the gut microbiome of the immunized mice. PNAG-based vaccine design guided by the well-defined synthetic library of PNAG is a powerful strategy to develop the next generation of vaccines and more effectively fight against pathogen infections including those by drug resistant strains.
Jennifer P. Collins, MD1; Samuel J. Crowe, PhD1; Ismael R. Ortega-Sanchez, PhD2; Lynn Bahta, MPH3; Doug Campos-Outcalt, MD4; Jamie Loehr, MD5; Rebecca L. Morgan, PhD6; Katherine A. Poehling, MD7; Lucy A. McNamara, PhD1 (View author affiliations)
What is already known about this topic?
Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. The pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) protects against N. meningitidis serogroups A, B, C, W, and Y and is licensed for use among persons aged 1025 years.
What is added by this report?
On October 25, 2023, the Advisory Committee on Immunization Practices recommended that MenACWY-TT/MenB-FHbp may be administered to persons aged 10 years when both a quadrivalent meningococcal conjugate vaccine (MenACWY) and meningococcal B vaccine (MenB) are indicated at the same visit.
What are the implications for public health practice?
MenACWY-TT/MenB-FHbp is the first pentavalent meningococcal vaccine approved for protection against serogroups A, B, C, W, and Y. Different manufacturers MenB vaccines are not interchangeable; when MenACWY-TT/MenB-FHbp is administered, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.).
Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDCs Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 1025 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 1623 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged 10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers serogroup Bcontaining vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.
Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. CDCs Advisory Committee on Immunization Practices (ACIP) recommends routine administration of a single dose of quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine (MenACWY) to persons at age 11 or 12 years, with a booster dose at age 16 years. ACIP recommends a 2-dose serogroup B meningococcal vaccine (MenB) series for persons aged 1623 years, based on shared clinical decision-making, to provide short-term protection against meningococcal disease caused by most serogroup B strains (1). ACIP also recommends routine vaccination with MenACWY (for persons aged 2 months) and MenB (for persons aged 10 years) who are at increased risk for meningococcal disease caused by the serogroups covered by each vaccine (Box) (1).
In October 2023, a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) was licensed for use in persons aged 1025 years (2). MenACWY-TT/MenB-FHbp contains the same components as those in two existing meningococcal vaccines: 1) N. meningitidis polysaccharide groups A, C, W, and Y conjugated to tetanus toxoid carrier protein (MenACWY-TT* [Nimenrix, Pfizer Inc.], a nonU.S.-licensed vaccine), and 2) two recombinant lipidated factor Hbinding protein (FHbp) variants from N. meningitidis serogroup B (MenB-FHbp [Trumenba, Pfizer Inc.]). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.
During June 2022October 2023, the ACIP Meningococcal Vaccines Work Group held monthly conference calls to review meningococcal disease epidemiology and evidence regarding use of MenACWY-TT/MenB-FHbp in persons currently recommended to receive MenACWY and MenB (policy question 1), MenACWY only (policy question 2), or MenB only (policy question 3). To guide deliberations, ACIP used the Evidence to Recommendations framework and considered the importance of meningococcal disease as a public health problem, benefits, and harms of MenACWY-TT/MenB-FHbp, values of the target population, acceptability, resource use, equity, and feasibility. ACIP evaluated the available evidence on the following prespecified benefits and harms (each with ranked importance), using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach (3): disease caused by serogroups A, B, C, W, and Y (critical); short-term immunity (critical); persistent immunity (important); serious adverse events (critical); nonserious adverse events (important); and interference with other recommended vaccines administered concurrently (important).
The body of evidence comprised data from three randomized, quadruple-blinded multisite clinical trials that assessed immunogenicity and safety** among healthy participants aged 1025 years. Participants were randomized to 1) the pentavalent group (2 doses of MenACWY-TT/MenB-FHbp, administered 6 or 12 months apart) or 2) the control group (MenACWY-CRM [Menveo, GSK, 1 dose] + MenB-FHbp [2 doses administered 6 months apart]) (4). The trials included ACWY-naive and ACWY-primed participants; all study participants were MenB-naive. The GRADE assessment focused on the 6-month pentavalent dosing interval for immunity outcomes; data on both 6- and 12-month pentavalent dosing intervals were assessed for safety outcomes.
Among both MenACWY-naive and MenACWY-primed participants, seroresponse for serogroups A, C, W, and Y 1 month after the first trial dose of ACWY-containing vaccine was achieved as often or more often in the pentavalent group than in the control group. On the basis of a composite measure, seroresponse for serogroup B 1 month after the second dose of serogroup Bcontaining vaccine was achieved more often in the pentavalent group than in the control group. The overall level of certainty for the critical outcome short-term immunity for all serogroups was moderate for healthy persons and low for persons at increased risk because of underlying medical conditions.
Among ACWY-naive and ACWY-primed participants, seroprotection for meningococcal serogroups A, C, W, and Y occurred as often or more often in the pentavalent group (48 months after receipt of 2 doses MenACWY-TT/MenB-FHbp) compared with the control group (54 months after 1 dose MenACWY-CRM). Little or no difference was observed in the frequency of serogroup B strainspecific seroprotection*** 48 months after receipt of 2 doses of pentavalent vaccine when compared with those seen 48 months after receipt of 2 doses of MenB-FHbp + 1 dose MenACWY-CRM. The overall level of certainty for this important outcome was low for serogroups A, C, W, and Y for healthy persons, moderate for serogroup B for healthy persons, and low for all serogroups for those at increased risk because of underlying medical conditions.
The proportion of participants who experienced serious adverse events was similar in the pentavalent group (0.6%) and the control group (0.5%; p = 0.7). No serious adverse events were deemed related to the vaccine by the study investigators. The pentavalent group had significantly fewer nonserious adverse events (24.6%) than did the control group (32.5%; p<0.001). The most common solicited adverse events within 7 days after receipt of either trial dose of MenACWY-TT/MenB-FHbp were injection site pain (84.4%89.3%; mostly mild or moderate), fatigue (47.6%52.1%; mostly mild or moderate), and headache (39.8%46.8%; mostly mild or moderate) (5). For both serious and nonserious adverse events, the level of certainty was low for healthy persons and very low for those at increased risk because of underlying medical conditions.
No data exist on coadministration of MenACWY-TT/MenB-FHbp with other vaccines. Review of the interactions sections of the package inserts for the component vaccines Nimenrix (MenACWY-TT) and Trumenba (MenB-FHbp) did not identify any concerns for coadministration with other vaccines (6,7).
Findings from two economic models (CDC model and Pfizer Inc. model) that assessed the health benefits and cost-effectiveness of MenACWY-TT/MenB-FHbp for each policy question within the routine schedule were considered by ACIP (8). According to the CDC model, strategies likely to be societally cost-saving would use the pentavalent vaccine to 1) replace a single dose of MenACWY and MenB when both are indicated, or 2) replace MenACWY and MenB when both are indicated, followed by completion of the 2-dose MenB series with a second dose of pentavalent vaccine. The CDC model also illustrated that when immunization against serogroup B meningococcal disease is not indicated, replacing both doses of MenACWY with the pentavalent vaccine would be incrementally less cost-effective. Despite differences in input values and assumptions, similar conclusions were reported by the Pfizer Inc. model.
ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for 1) healthy persons aged 1623 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine and 2) persons aged 10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia) (Table) (Figure). Indications for MenACWY and MenB vaccination have not changed since they were previously published (1).
For healthy persons, use of MenACWY-TT/MenB-FHbp should not supersede discussion of whether to administer MenB using shared clinical decision-making (Table). Clinicians should refer to previously published considerations for shared clinical decision-making and timing of MenB administration (1).
MenACWY products are interchangeable; the same vaccine product is recommended, but not required, for all doses (1). Different manufacturers MenB products are not interchangeable; administration of a B-component vaccine (monovalent or pentavalent) requires that all subsequent B-component vaccine doses, including booster doses, be from the same manufacturer. If one MenB dose was received but the vaccine manufacturer is not known, the series must be restarted with any licensed product to ensure completion of the MenB series using products from a single manufacturer.
If MenACWY-TT/MenB-FHbp is inadvertently administered in lieu of MenACWY or MenB when only one (i.e., MenACWY or MenB) was indicated, the dose can be considered valid if it would otherwise have been a valid dose of MenACWY or MenB (i.e., on the basis of indication, patient age, and dosing interval).
The licensed dosing interval for MenACWY-TT/MenB-FHbp is 6 months. Data are not available regarding safety or immunogenicity of MenACWY-TT/MenB-FHbp with dosing intervals exceeding 12 months. Healthy adolescents and young adults aged 1623 years who receive 1 dose of MenACWY-TT/MenB-FHbp on the basis of shared clinical decision-making should complete the MenB series with a dose of MenB-FHbp 6 months after the pentavalent vaccine dose was administered (Table).
Persons at increased risk for meningococcal disease who receive a dose of MenACWY-TT/MenB-FHbp and are recommended to receive additional doses of MenACWY and MenB <6 months after a dose of pentavalent meningococcal vaccine should receive separate MenACWY and MenB-FHbp vaccines rather than MenACWY-TT/MenB-FHbp (Figure). MenACWY-TT/MenB-FHbp may be used for booster doses in persons who remain at increased risk if a booster dose of both MenACWY and MenB are indicated at the same visit. MenACWY-TT/MenB-FHbp doses deviating from the licensed 6-month interval can be considered valid for MenACWY or MenB if the timing would otherwise have been valid for that component.
Severe allergy. MenACWY-TT/MenB-FHbp is contraindicated for persons with a history of severe allergic reaction, such as anaphylaxis, to any component of the vaccine or to a tetanus toxoidcontaining vaccine.
Pregnancy and breastfeeding. No data exist on use of MenACWY-TT/MenB-FHbp during pregnancy or while breastfeeding. Because limited data are available for MenB vaccination during pregnancy, vaccination with MenB should be deferred unless the pregnant person is at increased risk for acquiring meningococcal disease, and, after consultation with their health care provider, the benefits of vaccination are considered to outweigh the potential risks. When MenACWY is indicated, persons who are pregnant or breastfeeding should receive MenACWY-CRM or MenACWY-TT (MenQuadfi, Sanofi Pasteur).
Adverse events that occur in a patient after meningococcal vaccination should be reported to the Vaccine Adverse Event Reporting System (VAERS), even if it is uncertain whether the vaccine caused the event. Instructions for reporting to VAERS are available online at https://vaers.hhs.gov/reportevent.html or by telephone (800-822-7967).
Alison Albert, Isha Berry, Gabrielle Cooper, LeAnne Fox, Susan Hariri, Angela Jiles, Shelby Miller, Noele Nelson, Amy Rubis, Jeremiah Williams, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC; Jonathan Duffy, Tanya Myers, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, CDC; Andrew Leidner, Elisabeth Velazquez, JoEllen Wolicki, Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC; Jessica MacNeil, Melinda Wharton, Office of the Director, National Center for Immunization and Respiratory Diseases, CDC. Rosters of current and past members of the Advisory Committee on Immunization Practices are available at https://www.cdc.gov/vaccines/acip/members/index.html.
Katherine A. Poehling (Chair). Members: Lynn Bahta, Margaret Bash, Doug Campos-Outcalt, Jessica Cataldi, Paul Cieslak, Mark Connelly, Jeff Goad, Kathy Hsu, Francisco Leyva, Jamie Loehr, Karyn Lyons, Sharon McMullen, Rebecca L. Morgan, Amra Resic, David S. Stephens, Cacky Tate, Joseline Zafack.
1Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC; 2Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and Respiratory Diseases, CDC; 3Minnesota Department of Health; 4College of Medicine and Public Health, University of Arizona, Phoenix, Arizona; 5Cayuga Family Medicine, Ithaca, New York; 6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; 7Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Abbreviations: ACIP=Advisory Committee on Immunization Practices; MenACWY=quadrivalent (serogroups A, C, W, and Y) meningococcal vaccine; MenB=serogroup B meningococcal vaccine.
* https://pubmed.ncbi.nlm.nih.gov/33417592/
Abbreviations: MenACWY=quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine; MenACWY-TT/MenB-FHbp = Penbraya (Pfizer Inc.) pentavalent (serogroups A, B, C, W, and Y) meningococcal vaccine; MenB-FHbp=Trumenba (Pfizer Inc.) serogroup B meningococcal vaccine; MenB-4C = Bexsero (GSK) serogroup B meningococcal vaccine; NA=not applicable. * Assumes that a person has not previously been vaccinated with MenACWY or MenB. MenACWY vaccines are interchangeable; the same vaccine product is recommended, but not required, for all doses. Different manufacturers MenB vaccines are not interchangeable. https://pubmed.ncbi.nlm.nih.gov/33417592/ To determine catch-up vaccination recommendations for MenACWY and MenB, clinicians should see previously published recommendations. https://pubmed.ncbi.nlm.nih.gov/33417592/ Two-dose series with doses administered 1 month apart. ** Two-dose series with doses administered 6 months apart.
Abbreviations: MenACWY = quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine; MenACWY-TT/MenB-FHbp = Penbraya (Pfizer Inc.) pentavalent (serogroups A, B, C, W, and Y) meningococcal vaccine; MenB-FHbp = Trumenba (Pfizer Inc.) serogroup B meningococcal vaccine; MenB-4C = Bexsero (GSK) serogroup B meningococcal vaccine.
* MenACWY products are interchangeable; the same vaccine product is recommended, but not required, for all doses.
Different manufacturers MenB vaccines are not interchangeable.
To determine whether MenACWY and MenB are indicated based on a persons risk factors and timing of any previous meningococcal vaccines, clinicians should see previously published recommendations. https://pubmed.ncbi.nlm.nih.gov/33417592/
If MenB was received previously but the vaccine manufacturer is not known, the series must be restarted with any licensed product to ensure completion of the series using products from a single manufacturer. For additional guidance, clinicians should see previously published recommendations. https://pubmed.ncbi.nlm.nih.gov/33417592/
** If MenB-FHbp was received previously, MenACWY-TT/MenB-FHbp may be used provided the person has not received MenACWY-TT/MenB-FHbp previously or 6 months have passed since the previous dose of MenACWY-TT/MenB-FHbp.
Suggested citation for this article: Collins JP, Crowe SJ, Ortega-Sanchez IR, et al. Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged 10 Years: Recommendations of the Advisory Committee on Immunization Practices United States, 2023. MMWR Morb Mortal Wkly Rep 2024;73:345350. DOI: http://dx.doi.org/10.15585/mmwr.mm7315a4.
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There are many factors which affect how successfully a vaccine is rolled out. One of these is the public health communication strategy. Surprisingly, a key factor in determining the success of these strategies is religion. While some religious groups were keen to be vaccinated against COVID-19, others were much more hesitant.
During the height of the pandemic, getting vaccinated against COVID-19 quickly became the social norm. Having experienced pandemic life, most people were keen to get a full series of vaccinations as soon as they were made available.
Yet our new research, based on surveys of over 12,000 people found that there has been significant difference in vaccine uptake between religious communities.
Members of the Methodist and Church of England denominations are more likely to have been vaccinated, while Pentecostal, evangelical and Muslim respondents have received far fewer vaccinations. Methodists, on average, have had 3.48 vaccinations, while Pentecostals have only had 1.88.
Why is this the case? This is the difficult part of the story. We know that some minority groups have faced discrimination and this, in turn, can lead to lower levels of trust in authority figures. For instance, our recently published research shows that ethnic minorities have lower levels of trust in the NHS.
In terms of religion, we have noticed some unusual trends. Members of the Pentecostal denomination have high levels of trust in medical doctors but low levels of trust in scientists. This is an area we hope to explore further in future research.
Once we accept that there are differences in vaccine uptake across religions, we can then move on to the equally difficult question of what to do about it. We argue that health authorities, such as the NHS, need to actively engage with religious leaders and religious communities.
There are examples of community-based success stories. For instance, early in the pandemic, mosques in Birmingham were used as vaccination centres. This kind of religious community engagement in public health can be of vital importance.
Amid concerns during the pandemic that ethnic minority groups were more likely to be targeted with misinformation (sometimes from faith leaders outside the UK) and to be hesitant about getting vaccinated, religious leaders were deployed with great success. They were well placed to counter inaccurate information and encourage vaccine uptake.
We argue that there needs to be more formal recognition of such community-based public health messaging. When there are such stark differences in a vital area of public health such as vaccination, we really need health bodies to do all they can to reach out to the community. Sometimes, as in the case with religion, they cannot do this themselves with a traditional top-down communication model; they need to work with religious leaders.
Theres still much that we dont know. For instance, the interplay between religion and ethnicity is complex. This is an area we intend to explore in more depth in future research.
Apart from some notable exceptions, religion is often something of an elephant in the room in the political sphere. It is easy to see how it could also be ignored in a public health setting and perhaps why it became an issue during the COVID-19 vaccination rollout.
The NHS is clearly a secular organisation, and there would be no desire to change that. But we cannot ignore that, in terms of COVID-19 vaccine rollout, certain religious communities have been let down, or left behind. Future public health campaigns need to acknowledge this and find ways to overcome it.
Tetanus is vaccine-preventable, yet it kills tens of thousands of infants worldwide every year
The dawn was slowly rising over the village of Abaradjou in the health district of Sankor in Mali's Tombouctou region. Once flourishing, the region was struggling with maternal and neonatal tetanus (MNT), an acute infectious disease that threatens the survival of mothers and their infants.
Caused by a bacterium found in the soil and in animal droppings, MNT results from the contamination of the umbilical stump during unhygienic cord care at childbirth. Symptoms usually occur from the third day in a newborn who was normal and suddenly becomes rigid, presenting with uncontrollable convulsions and muscle spasms. Without medical care, the mortality rate is nearly 100 percent.
In this neighborhood, as elsewhere in Mali, deliveries were often performed by traditional midwives, using contaminated equipment. This practice, coupled with adherence to ancient rituals, unfortunately made tetanus contamination all too common during deliveries.
Aissata, a 46-year-old resident of Abaradjou, was determined to change her fate. Having already lost a baby to this disease, she resolved not to let history repeat itself.
They did everything they could, but the baby passed away. The doctor explained to me that it was tetanus and that if I had been vaccinated during pregnancy, it could have saved my baby. Losing a child is terrible and I wouldn't wish it on any parent. Aissata, a 46-year-old mother in Mali
"I gave birth at home assisted by a grandmother," says Aissata. "A few days later, the baby couldnt breastfeed, and his condition was getting worse. So, I took him to the health center. They did everything they could, but the baby passed away. The doctor explained to me that it was tetanus and that if I had been vaccinated during pregnancy, it could have saved my baby. Losing a child is terrible and I wouldn't wish it on any parent."
Aware of the risks, Aissata sought out information and learned from a women's group in her village about a new initiative by the Malian government, with support from UNICEF and WHO, targeting the elimination of maternal and neonatal tetanus. Inspired by the possibility of a different ending for her story, Aissata decided to actively protect any future pregnancies by getting the tetanus vaccine.
The very next day, as if in answer to her determination, an advanced strategy team arrived by motorcycle in Aissatas village to administer the tetanus vaccine to all women of reproductive age (pregnant or not). Aissata was among the first to receive her dose and made the significant choice to travel to the Sankor community health center for the remaining doses of the vaccine. The road was long and arduous, but the hope of a better outcome for her future pregnancies sustained her.
"Today I am talking about my story to the women in my village and I am telling them to get vaccinated against tetanus and to have check-ups during pregnancy. When I talk about my story, some tell me that they have also lost babies following home births." recounts Aissata, after finishing an educational talk with other women from her village.
Today I am talking about my story to the women in my village and I am telling them to get vaccinated against tetanus and to have check-ups during pregnancy. Aissata
In 2023, the World Health Organization (WHO) announced that Mali had officially eliminated maternal and neonatal tetanus, a major advance for public health in a country where maternal and infant mortality rates are among the highest in the world.This status was confirmed following a detailed evaluation, which demonstrated that Mali meets WHO's standard of having less than one case of neonatal tetanus per 1,000 live births in each of its health districts.
Mali's significant milestone is a testament to the collective efforts of the country and its partners, including UNICEF. A comprehensive strategy to strengthen systematic vaccination played a pivotal role. Health centers across Mali were equipped with solar refrigerators to store vaccines efficiently, and provided with motorcycles and vehicles to facilitate the delivery of vaccination services.
Vaccinations were administered through a well-organized approach: at health facilities for fixed strategies, by motorcycle for areas located between 5 and 15 kilometers away, and through mobile clinics for communities more than 15 kilometers from a health facility.
From 2002, Mali embarked on several vaccination campaigns against tetanus, adopting fixed, advanced and mobile strategies. These efforts were significantly supported by financial contributions from the United States, underscoring the global commitment to combatting MNT. The vaccination program proved to be a lifeline for thousands of women, including Aissata.
Childbirth practices in Mali also saw remarkable improvements through the gradual introduction of qualified personnel including gynecologist-obstetricians, midwives and obstetric nurses into health centers and district hospitals. This initiative was supported by the state and partners like the World Bank to enhance the quality of maternal care.
Traditional midwives, integral to many communities, received training on essential hygiene practices to further reduce the risk of tetanus contamination. The training emphasized the importance of maintaining clean surfaces, hands and clothes during childbirth, using a new blade for umbilical cord cutting, applying chlorhexidine for cord care and avoiding the application of potentially harmful substances on the umbilical wound. Through these comprehensive measures, Mali has made significant strides in safeguarding the health of mothers and newborns against tetanus.
These practices have saved millions of women of childbearing age and newborns while protecting them against tetanus, explains Dr. Moumini Guindo, a physician at the Sankor community health center.
Aissata's determination and resilience are a symbol of the possibility of change and the power of taking proactive steps towards health and safety. In this region of Mali, her fight against MNT, marked by courage and transformation, serves as an inspiration for many women a new dawn for an era of health awareness and empowerment in the community.
UNICEF has immunized millions of women all over the globe, with support from partners like Kiwanis International and The Church of Jesus Christ of Latter-Day Saints, in an effort to eliminate tetanus in dozens of countries. As of December 2023, MNT remains endemic in just 11 countries.
Help UNICEF deliver vaccines to protect children from deadly diseases.
This story was originally published on unicef.org
A new oral vaccine for cholera has received prequalification by the World Health Organization (WHO) on 12 April. The inactivated oral vaccine Euvichol-S has a similar efficacy to existing vaccines but a simplified formulation, allowing opportunities to rapidly increase production capacity.
The new vaccine is the third product of the same family of vaccines we have for cholera in our WHO prequalification list, said Dr Rogerio Gaspar, Director of the WHO Department for Regulation and Prequalification. The new prequalification is hoped to enable a rapid increase in production and supply which many communities battling with cholera outbreaks urgently need.
WHO prequalification list already includes Euvichol and Euvichol-Plus inactivated oral cholera vaccines produced by EuBiologicals Co., Ltd, Republic of Korea, which also produces the new vaccine Euvichol-S.
Vaccines provide the fastest intervention to prevent, limit and control cholera outbreaks but supplies have been at the lowest point amidst countries facing dire shortcomings in other areas of cholera prevention and management such as safe water, hygiene and sanitation.
There were 473000 cholera cases reported to WHO in 2022 -- double the number from 2021. Further increase of cases by 700 000 was estimated for 2023. Currently, 23 countries are reporting cholera outbreaks with most severe impacts seen in the Comoros, Democratic Republic of the Congo, Ethiopia, Mozambique, Somalia, Zambia and Zimbabwe.
(WTTW News)
The Chicago Department of Public Health is recommending medical providers consider administering a second dose of the measles vaccine to children earlier than usual, following community spread of measles in the last several weeks, the agency said Friday.
The city has seen 64 measles cases since early March, after not having a confirmed case of the virus in almost five years. Eleven new measles cases have been reported so far this month, with a peak in reported cases occurring in late March, according to CDPHs measles dashboard.
Measles cases in Chicago account for more than half of reported cases in the U.S. so far this year. More than half of the measles cases in the city were in children ages 4 or younger.
Most of the measles cases are connected to a migrant shelter in Pilsen; however, city health officials are also warning of measles cases in the broader community.
We need everyone whether a new arrival or a longtime Chicagoan to ensure they and their family members are up to date on their vaccinations, CDPH Commissioner Dr. Olusimbo Simbo Ige said in a statement. Too many Chicagoans are still not vaccinated against this highly contagious virus and other vaccine-preventable diseases.
The measles-mumps-rubella vaccine, or MMR vaccine, is considered highly effective at preventing measles. One dose of the vaccine typically given at 12 to 15 months of age is about 93% effective against the disease. A second dose typically given at 4 to 6 years of age bumps the efficacy up to 97%.
Now, CDPH is recommending medical providers consider administering the second MMR dose to Chicago children over 12 months of age on an earlier schedule as soon as 28 days after a first dose especially if those children are attending school or day care.
When we see community transmission, well oftentimes take a measure to boost that immunity with the second shot, said Dr. Larry Kociolek, pediatric infectious diseases physician at Lurie Childrens Hospital. Thats something providers can discuss with their patients and determine if thats the right measure for them.
Children who receive two appropriately timed MMR doses before 4 years of age should not need any additional doses in their lifetime, the city health department said.
So far, CDPH has reported administering more than 17,000 measles vaccine doses to Chicago residents, including newly arrived migrants at the Pilsen shelter, since the start of the measles outbreak on March 7.
(Its) hard to tell the end of an outbreak, but we certainly see the protection of this community in the setting and were certainly at the tail end of those cases presenting, Massimo Pacilli, deputy commissioner of the disease control bureau at the Chicago Department of Public Health, said during a media briefing last week.
Measles is a highly contagious, airborne respiratory infection that can lead to pneumonia and other serious complications. Symptoms of measles include rash, high fever, cough, runny nose and red and watery eyes.
While cases of measles are rare in Chicago due to high vaccination coverage from childhood, CDPH said, measles cases have been increasing recently in the U.S. and can be dangerous to those who are unvaccinated, especially babies and young children.
The increase in measles cases in Illinois, and in several other U.S. states, is a fairly predictable consequence of slowly declining vaccine rates all over the country, Kociolek said.
The MMR vaccine is available at most doctors offices and pharmacies. Additionally, CDPHs immunization clinics provide the MMR vaccine for no out-of-pocket cost to any child through 18 years of age and uninsured adults 19 and older.
Contact Eunice Alpasan:@eunicealpasan| 773-509-5362 |[emailprotected]
