After cow-to-cow transmission of avian influenza A subtype H5N1 in US dairy herds led to a cow-to-human transmission in Texas, the Association of State and Territorial Health Officials convened a panel of experts for a scientific symposium on Thursday to talk about the public health implications.
"The risk to the general public remains low," said Vivien Dugan, PhD, director of the Influenza Division at the Centers for Disease Control and Prevention (CDC). And should there be an outbreak, vaccine development measures are in place, she added.
From the sequencing data, "we can expect and anticipate that [the candidate vaccine viruses] will provide good protection," she explained.
Establishing candidate vaccine viruses "are the precursor to moving into large-scale vaccine production," Dugan explained. Should that be needed, the candidate viruses can be used by manufacturers to produce new vaccines.
The CDC is also actively partnering with commercial diagnostic developers and testing companies in case there is a need to scale-up testing, Dugan said.
The only current human case in the United States was reported on April 1 and confirmed by the CDC within 24 hours, reported Sonja Olsen, PhD, associate director for preparedness and response of the Influenza Division at the CDC.
The person had direct exposure to cattle and reported eye redness, consistent with conjunctivitis, as the only symptom. The person received treatment and has recovered, and there were no reports of illness among the person's household contacts, Olsen said.
The only other detection of the virus in a human in the United States was in 2022 and it was associated with infected poultry exposure. That person also had mild illness and recovered, Olsen explained.
Since 1997, when the first case of human infection was reported globally, "there have been 909 [human cases] reported from 23 countries," Olsen said. "About half [52%] of the human cases have resulted in death." Only a small number of human cases have been reported since 2015, but since 2022, more than two dozen human cases have been reported to the World Health Organization.
Experience with the virus in the United States has been about a year behind that in Europe, said Rosemary Sifford, DVM, chief veterinary officer at the US Department of Agriculture. In the United States, the first detection in January 2022 was in wild birds; this was followed the next month by the first detection in a commercial poultry flock.
In March of this year, the United States had its first detection in cattle, specifically dairy cattle. But testing has shown that "it remains very much an avian virus. It's not becoming a bovine virus," Sifford reported.
Earlier this week, in an effort to minimize the risk of disease spread, the USDA issued a federal order that requires the reporting of positive influenza tests in livestock and mandatory testing for influenza of dairy cattle before interstate movement.
"As of today, there are affected herds in 33 farms across eight states," reported Olsen.
Tests are ongoing to determine how the virus is traveling, but "what we can say is that there's a high viral load in the milk in the cattle, and it appears that the transmission is happening mostly within the lactating herds," Sifford reported. It is unclear whether that is happening during the milking of the cows or whether contaminated milk from a cow with a high viral load is transmitting the virus to other cattle.
"We are strongly encouraging producers to limit the movement of cattle, particularly lactating cattle, as much as possible," she says.
"We haven't seen anything that would change our assessment that the commercial milk supply is safe," says Donald Prater, DVM, acting director of the Center for Food Safety and Applied Nutrition at the US Food and Drug Administration (FDA).
In the federal and state milk safety system, he explained, nearly 99% of the commercial milk supply comes from farms that participate in the Grade A program and follow the Pasteurized Milk Ordinance, which outlines pasteurization requirements.
Because detection of the virus in dairy cattle is new, there are many questions to be answered in research, he reported. Among them:
A critical question regarding the potential risk to humans is how much milk would have to be consumed for the virus to become an established infection. That information is essential to determine "what type of pasteurization criteria" are needed to provide "acceptable public health outcomes," Prater said.
The CDC is currently using the flu surveillance system to monitor for H5N1 activity in people. The systems show no current indicators of unusual influenza activity in people.
Immunization with inactivated vaccines while receiving the disease-modifying therapy natalizumab for highly active multiple sclerosis (MS) is safe and immunogenic, with no increased risk for disease progression, new research shows.
The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.
On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.
"We observed seroprotection rates exceeding 90% for hepatitis A, hepatitis B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected," lead author Ren Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autnoma de Barcelona, Barcelona, Spain, told Medscape Medical News. "This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses."
The study was published online on April 12 in JAMA Network Open.
Today's high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers note.
As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression.
Reports of disease worsening following vaccination "have raised controversy around vaccine safety," the authors write. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.
The motivation for the study "stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination," Carvajal said.
Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.
Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).
The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.
They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.
The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.
There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P= .004) and median number of new T2 lesions (P = .01).
There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
'Viable Option'
The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.
The algorithm is "integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections," Carvajal said.
Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.
This suggests that using natalizumab for a brief duration might be a "viable option to contemplate," the authors noted.
Commenting on the findings for Medscape Medical News, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study "demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity as measured by antibodies is preserved in MS patients who receive natalizumab."
This "contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments," said Gombolay, who was not part of the study. "If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option."
"However, this must be balanced with other considerations," she added, including the risk for PML and pregnancy.
This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Carvajal reported receiving grants from Vall d'Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work.Gombolay serves as media editor forPediatric Neurology and as associate editor of theAnnals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.
Batya Swift Yasgur MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).
The latest data from the European Centre for Disease Prevention and Control (ECDC) reveal a concerning uptick in vaccine-preventable diseases such as measles and pertussis across Europe, following decreased levels throughout the COVID-19 pandemic period. The findings were released as part of the 2024 European Immunization Week, taking place April 21-27, and emphasize a critical need for heightened vaccination campaigns to protect public health.
After a period of low activity between 2020 and 2022, the number of measles cases began increasing in 2023, persisting across several EU member states. From March 2023 to February 2024, more than 5770 measles cases were reported, with at least five deaths.
Infants younger than 1 year face the highest risk owing to their inability to receive vaccinations, relying on immunity in the community for protection. Measles, known for its high transmissibility, necessitates that at least 95% of a population receive two doses of measles-containing vaccine to halt transmission.
A surge in pertussis cases also emerged in mid-2023 across various EU/EEA countries, with preliminary data indicating a more than 10-fold increase compared with 2022 and 2021. Newborns and infants, who are vulnerable owing to incomplete vaccination, face heightened risks for severe illness and mortality. Timely administration of all recommended pertussis-containing vaccines is imperative to safeguard this group, with vaccination during pregnancy offering additional protection for young infants.
"The measles and pertussis outbreaks are just two examples [showing] that, despite the dramatic decrease in cases and mortality over the past decades, different vaccine-preventable diseases continue to circulate and still inflict suffering in those unprotected or vulnerable," cautioned Andrea Ammon, director of the ECDC, during a press conference.
Mumps: Although considered minor, the uptick in mumps cases warrants attention. In 2022, 27 EU/EEA countries collectively reported 2593 cases of mumps, marking an increase in the overall notification rate from 0.4 to 0.7 case per 100,000 population compared with 2021.
Diphtheria: This disease remains rare in EU/EEA countries, yet 2022 saw a concerning rise with 359 reported cases, which were predominantly cutaneous diphtheria. Notably, more than 60% of diphtheria cases occurred in a country different from the one in which they were notified, indicating potential challenges in surveillance and response.
Invasive meningococcal disease: In 2022, a surge in invasive meningococcal disease was recorded across all EU/EEA countries, totaling 1149 confirmed cases and resulting in 110 deaths. This marks a stark increase from 2021, in which 612 cases and 48 deaths were reported.
As outbreaks of vaccine-preventable diseases persist across EU/EEA countries, concerted efforts are imperative to pinpoint immunity gaps within the population, particularly among individuals who may have missed or postponed their vaccinations. Action is required to ensure equitable access to vaccinations, particularly among vulnerable and marginalized groups such as refugees, migrants, and asylum seekers.
The ECDC reaffirmed its commitment to bolster national vaccination programs and to uphold vaccine quality, safety, and efficacy, while striving for universal and equitable access for all.
Ammon emphasized that EIW, which takes place across Europe every year in the final week of April, serves as an opportunity to reflect on the monumental impact vaccines have had and continue to have on people worldwide and their role in overall health and well-being across all age groups. The European Region of the World Health Organization has designated "Protecting Generations" as the theme of EIW 2024, commemorating 50 years of the Essential Programme on Immunization.
"Achieving and maintaining high vaccination uptake, disease surveillance, and prompt response actions to control outbreaks remain the key actions against these diseases. Vaccines have protected many generations, and we should ensure that this continues to be the case," Ammon said.
MONTGOMERY The Alabama House of Representatives passed legislation on Thursday requiring parental consent for minors to receive vaccinations.
Under current Alabama law, any minor who is over the age of 14 or a high school graduate can give legal consent to any authorized medical, dental or mental health treatment without the permission of a parent or guardian.
House Bill 165 (HB165)by State Rep. Chip Brown (R-Hollinger's Island) would add a short caveat to the existing law, stating that "an unemancipated minor may not give consent to the administration of a vaccination for himself or herself without the written consent of a parent or legal guardian." Regarding Alabama law, Brown's bill would raise the age of informed consent to 19 for vaccinations.
Brown presented the bill before the House, amending the legislation to account for cases where the minor is not reliant on a parent or guardian for support, living apart from their parent or guardian, or managing their own affairs.
Brown described an event in an Alabama school where he claimed there was a mass administration of flu vaccines without parental notification or consent.
Newly elected State Rep. Marilyn Lands (D-Huntsville) opposed the bill, claiming it was "government overreach."
"I'm particularly concerned about the HPV vaccine," Lands said. "The reality is, there are families, there are situations where a child wants to get that vaccine, and their father is the rapist. So, there are many kinds of instances where I think children should be able to consent for themselves."
State Rep. Brett Easterbrook (R-Fruitdale) responded to Lands from the podium.
"It's government overreach for someone to give a child a vaccine without the parent's permission, that is government overreach," Easterbrook said. "It has nothing to do with a rapist; I don't think there's a vaccine for rape. They are still required to report rape and abuse. But the idea that the government should decide for the parent which vaccine the kid should and should not take is what I see as government overreach."
Republican lawmakers overwhelmingly supported the legislation.
"I was just going to tell you, as a parent of six children, I appreciate what you're doing here," said State Rep. Shane Stringer (R-Citronelle). "I absolutely want to be notified of something like this involving my children. Not that it's a bad thing, a flu vaccination or COVID or anything else, but I absolutely want to be notified and given the opportunity to have input on what my child receives or not."
State Rep. Ernie Yarbrough (R-Trinity) applauded the bill for returning parental rights in the aftermath of the COVID-19 pandemic.
"Besides so many attacks on parental rights and circumventing the nuclear family in libraries and other things, our country is in these battles," he outlined. "Through all the situations of COVID and vaccine mandates and all the things that have happened, it's important that we establish the foundation of reasserting individual and family rights and freedoms."
The bill ultimately passed with a vote of 81-17 with three abstentions. The "no" votes came exclusively from Democrats.
To connect with the author of this story or to comment, email craig.monger@1819news.com.
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The Imvanex vaccine is one of two available vaccines that are used to protect against the mpox virus. Vaccines were widely used during the 2022 mpox outbreak. But currently no vaccines are available in the Democratic Republic of Congo, which has reported thousands of cases so far this year. Alain Jocard /POOL/AFP via Getty Images hide caption
The Imvanex vaccine is one of two available vaccines that are used to protect against the mpox virus. Vaccines were widely used during the 2022 mpox outbreak. But currently no vaccines are available in the Democratic Republic of Congo, which has reported thousands of cases so far this year.
In the Democratic Republic of Congo, the fight against mpox previously known as monkeypox is entering a new phase.
While many are anxious to contain the outbreak the largest mpox outbreak ever recorded in the DRC with more than 4,500 cases so far this year experts say that's not yet possible: There are no vaccines or treatments in the country right now, and even the testing capacity is severely limited. Instead, this new phase of the mpox fight involves simply getting a better understanding of what exactly is going on.
"We've been doing a lot of groundwork and building support and trying to strengthen things. And now, I hope, we're at a pivot point," says Dr. Jennifer McQuiston of the U.S. Centers for Disease Control and Prevention. "Over the next three weeks, we expect to learn a lot about what's happening on the ground."
The CDC has worked with the DRC for 15 years but has increased their efforts in response to the current mpox outbreak, as has the World Health Organization. They've helped the DRC expand its testing capacity by opening labs in some of the most affected, remote areas. The CDC has also helped fund local epidemiological teams that can provide a more granular understanding of mpox cases.
The DRC's mpox outbreak is noteworthy not only for its size but for the changing nature of the virus.
According to Africa CDC, 11 African countries have reported mpox cases but the DRC is the clear epicenter, with a caseload three times what it was this time last year. The virus, which usually jumps from a small animal to a human and then spreads between people, causes painful lesions and sometimes fever, malaise and even death.
The concern is heightened because the type of mpox circulating, called Clade I, is 10 times deadlier than the type of mpox that caused a worldwide outbreak in 2022. About 10% of Clade I cases are fatal; DRC has confirmed 311 mpox deaths this year. In addition, early evidence suggests there is a new strain of the mpox virus in the eastern part of the DRC that's circulating among sex workers and seems to be sexually transmitted. Clade I has never been known to transmit sexually.
Other countries and international organizations have been working to balance their desire for quick action against the DRC's right to address its own health plans and priorities. The nation is juggling a number of pressing health challenges, including measles, cholera and plague.
"We have work to do," says Dr. Mandy Cohen, the director of the CDC. "[We] have to work with a sovereign country. And they have a lot of health threats... And so helping them work through not just mpox but their overall response is really what we're trying to do."
Earlier this month, the Africa Centres for Disease Control and Prevention the public health agency of the African Union helped convene a high-level emergency meeting on mpox in Kinshasa, DRC. The meeting brought together hundreds of experts.
By the end of the meeting, the DRC had announced its intent to use vaccines against mpox although it still needs to approve the vaccines and draw up a strategy for delivery. In addition, the DRC said it would work quickly to approve a treatment option.
Vaccines have been used to combat mpox outbreaks in other places, including the U.S., Europe and Japan. So far, they have not been approved for use in most African nations.
One challenge is that there is very limited data on how the vaccines work in children who represent the majority of mpox cases in the DRC and also minimal data on its use in populations that deal with other health issues, like malnutrition. In March, the WHO's vaccine advisory committee recommended the off-label use of the mpox vaccine in children but urged further study.
There are also major logistical challenges to rolling out an mpox vaccination effort, given that most of the cases are in remote areas and parts of the country face violent unrest. Now that the DRC has declared its intent to use two types of mpox vaccines, its National Regulatory Authority is meeting for a vaccine assessment. While mpox vaccines are likely months away, these steps are being heralded as progress as is the country's acknowledgement of the scale of the concern.
"This situation constitutes a public health emergency," said Samuel-Roger Kamba, the Minister of Health in the DRC, speaking in French at the Africa CDC meeting's closing ceremony. "The Democratic Republic of Congo remains very concerned by the scale and severity of the mpox epidemic which is raging in 23 of the country's 26 provinces."
Nicaise Ndembi, a virologist and senior adviser to the director-general of the Africa CDC, says that, so far, that speech has not been followed by an official declaration of a health emergency. "Meetings are meetings, right? Except if we really take action," he tells NPR.
Ndembi says there are a lot of considerations that come into play before an official declaration can be issued. Many countries vividly and bitterly remember how travelers from numerous African countries were banned after Botswana and South Africa shared news about the discovery of Omicron, which was then a new strain of COVID. These bans cost the countries economically and drew criticism since simultaneous cases in Europe did not receive the same response. "So, it's very sensitive," he says.
Nonetheless, Ndembi says his instinct is that the scientific evidence merits a health emergency, particularly because the DRC borders nine countries and the virus could spread through travelers as it did in 2022.
"I would say: Declare! Because, by declaring, you have access to the drugs, you have access to the vaccines. We don't need to go through all the approval processes. And that will open the door for international support to mobilize resources," he says.
But in the interim, there are steps that can be taken, including disease surveillance, emergency response communication, infection prevention control and improved clinical care, even without mpox treatments in the country, says Dr. Rosamund Lewis, the WHO's technical lead and emergency manager for mpox.
"Small children [with mpox] can become dehydrated very quickly. When you have enlarged lymph nodes in the neck and sores in the mouth, children can't eat or drink. So without access to rehydration methods, nasogastric tubes, intravenous [fluids] if needed without basic medical care that you would take for granted anywhere else the children have a very high risk of severe disease and death, which we're seeing in the data," explains Lewis.
"Our responsibility, as a global community, is to support and accompany the DRC in their actions," she says.
"I will remind everyone that in two and a half, three years of mpox response, there hasn't been a single penny of donor money invested at a global level for controlling mpox," adds Dr. Michael Ryan, executive director of the WHO's Health Emergencies Programme. "So while the concerns of the world are very well known, I don't see the concerns of the world reflected in the investment of resources needed to actually contain this virus."
In vaccine production, QC is an important step to confirm identities of raw materials, relevant ingredients and final products. They are also screened for unwanted contaminants within the QC processes25,26. In case of SARS-CoV-2 vaccine production, the presence of other viral strains in the drug substances and/or end products would lead to failure of product tests and may cause a drop in efficacy and/or increase the risk of adverse events27. Therefore, establishing a suitable method for checking authenticity of the SARS-CoV-2 strain selected for vaccine production and detecting contaminants from other strains is essential for vaccine quality assessment. LCMS technique is widely known for its sensitivity, robustness, accuracy and high throughput28. It has a benefit over an enzyme-linked immunosorbent assay (ELISA) because it can detect several peptides from one or multiple viral strains in a single run29. LCMS method has been broadly used in clinical research to identify SARS-CoV-2 variants, but surprisingly its application in manufacturing process of biological products has less been found30. This study demonstrated that LCMS can be a useful tool for evaluating product quality in biopharmaceutical production.
Wuhan and early developed SAR-CoV-2 strains, for example Alpha, Beta, Gamma, Delta and Epsilon show little variation among their RBD amino acid sequences, demonstrating their close relationships. However, more recently emerging Omicron strains show 17 amino acids different from Wuhan wild type, indicating substantial evolution of Omicron lineages (Fig.1). All distinct amino acids detected among 14 SARS-CoV-2 strains contribute to nine characteristic peptides upon tryptic digestion. Most of the characteristic peptides can be readily detected in LCMS analysis but unmodified peptide 6 is hardly detected. The sequence between 150D and 192R positions (43 amino acids in length) has neither arginine (R) nor lysine (K), digestive sites of trypsin enzyme, causing a lengthy peptide after digestion. The large peptide could become low hydrophilicity, poor ionization, limited fragmentation and could comprise multiple charge states, resulting in low or no signal in LCMS analysis31,32. In the RBD-Fc sequences of different SARS-CoV-2 strains, including Delta, Iota, Theta and Eta strains, T161 or E167 position is substituted with K, yielding digestible peptides, which are useful for differentiating these strains from the others and from each other (Fig.3). Peptides 1, 2, 3, 4 and 7 are applicable for detecting Omicron BA1 and BA2. Peptide 3 is helpful for identifying Beta and Gamma strains. Peptides 8 and 9 are required for identifying Zeta and Alpha strains, respectively. Peptide 5 is unique for Lambda strain and applicable for distinguishing Kappa and Epsilon strains from the others. When all characteristic peptides were used together (Fig.3) and the identification processes were followed step by step from the top to the bottom, identification of SAR-CoV-2 strains can be achieved in a single attempt, even from a mix of recombinant RBD-Fc proteins derived from different viral strains (Fig.4).
However, Kappa and Epsilon strains cannot be differentiated from each other with this LCMS method because they have only one amino-acid difference, which does not contribute to a characteristic peptide after tryptic digestion. To overcome this issue, GluC protease could be an alternative enzyme for using alone or together with trypsin enzyme to additionally cleave the proteins at C-terminus of glutamic acid (E). GluC enzyme could facilitate the differentiation of SARS-CoV-2 RBD-Fc proteins derived from Epsilon and Kappa strain because the sequence of Epsilon strain contains glutamic acid at position 167 (E167), which is cleavable by GluC enzyme. However, this amino acid is mutated to glutamine (Q167) for Kappa strain. After GluC digestion, the resulting peptides would be different between the samples derived from Epsilon and Kappa strains and therefore distinguishable by LCMS analysis. Apart from GluC enzyme, other proteases, such as LysC, ArgC and AspN enzymes, could be additionally applied to increase completeness of protein digestion at lysine (K) and arginine (R) positions or additionally cleave the peptide at aspartic acid (D) position to increase number of resulting peptides. This could lead to better detection and differentiation of vaccine products derived from closely related SARS-CoV-2 strains. However, time and cost would be factors of concern as increased number of enzymes will double digestion time and chemical use.
Post-translational modifications of N-glycosylation could be another factor, affecting LCMS results and analytical performance to confirm protein identity and detect contaminations. In this study, characteristic peptide 1 has one glycosylation site at N26 amino acid. Sometimes, MS/MS signal of the non-glycosylated form was not observed. Peptide 1 is important for differentiating RBD-Fc proteins derived from Omicron BA1 and BA2 from the others. To improve the MS/MS signal of peptide 1 and abate the effects of N-glycosylation, protease enzymes, such as Endo-S and PNGase A, could be additionally used to release N-glycans from the core protein structure. Nonetheless, other characteristic peptides, including peptides 2, 3, 4 and 7, are appliable for distinguishing Omicron BA1 and BA2 strains from each other and from the others. Hence, Endo-S and PNGase A enzymes might not be necessary in this study, but they would benefit the other studies, discovering that only N-glycosylated peptide is a characteristic peptide.
In typical LCMS analysis, the resulting peptides are matched to the reference sequence of individual proteins. For example, the result from Wuhan SARS-CoV-2 RBD-Fc sample is usually compared against the reference amino acid sequence of Wuhan strain only (Fig.2). Identity of Wuhan strain might be confirmed but potential contaminants from other strains would not be identified. By having the peptide key alongside the reference of target protein, purity of intermediate substances and vaccine products can be more ascertained. Generally, the limit of LCMS detection is in a range of 110ngml1 solution or ng mg1 protein33,34. Within this study, a protein spike-in assay was performed to examine the limits of peptide detection. Among nine characteristic peptides, the lowest points of peptide detection at MS/MS level were around 5ngml1, observed from peptide 5 and 8 (Table 1). These two peptides are unique for detecting RBD-Fc derived from Lambda, Zeta, Epsilon or Kappa strains. Peptide 3 for detecting RBD-Fc derived Gamma strain and peptide 6.1 for detecting RBD-Fc derived from Iota strain were detectable at concentration around 20ngml1, demonstrating relatively sensitive detection by this developed LCMS method. Detection limits of other peptides were in a range of 50200ngml1, which would be sufficient for detecting even small contaminations in our vaccine production. Contaminants from other strains likely occur at microgram level since the tested materials are typically prepared at 1mgml1.
According to the WHO guideline, cross-contamination of biological materials at any stage during biopharmaceutical manufacturing is a risk and must be assessed and controlled19. In our production system, biological materials can be derived from different SARS-CoV-2 strains, therefore appropriate logistic plans and activities, such as a clear separation of storage areas between different bacteria cell banks and avoiding infiltrating different strains at the same time, must be exercised to reduce the risk. These processes have already been implemented in the manufacturing plant of Baiya Phytopharm. An implementation of LCMS analysis in the QC process will ensure the purity of starting materials and final vaccine products. Furthermore, molecular techniques, such as real-time PCR, could be further developed to check contaminations of different SARS-CoV-2 strains in bacterial clones and DNA plasmids during cloning and transformation steps. It could also be used to track down microbial contaminations and host cell DNA residues in the final vaccine products35. By using bioanalytical and molecular techniques in combination, QC analysis in biologic manufacture would be more forceful to ensure production integrity and product quality.
Vaccines are the most effective way of preventing infectious disease and saving lives.
The Expanded Programme on Immunization (EPI), launched by the World Health Organization in 1974 in response to high rates of vaccine-preventable disease worldwide, was a significant milestone in public health. By reaching communities around the world with life-saving vaccines, the programme has contributed to an enormous reduction in preventable diseases.
The EPI helped eliminate smallpox, fight polio and massively reduce child mortality. After 50 years of its existence, an analysis published in The Lancet today show just how far-reaching the impact of the programme has been. This framework estimates deaths averted, years of life saved and years of full health gained for 14 pathogens within the EPI portfolio.
The analysis builds upon infectious disease modelling estimates produced by the Vaccine Impact Modelling Consortium (VIMC) and the Global Burden of Disease study (GBD).
Here are five key achievements.
Between 1974 and 2024, 40% of the global reduction in infant mortality is attributable to vaccination (this benefit goes up to 52% in Africa). Improvements in water, sanitation and hygiene, better nutrition and other factors have improved health and reduced the spread of disease since the 1970s, but vaccination has made the biggest single contribution to the prevention of deadly infections.
Where vaccines have been able to stop transmission, vaccination of a critical number of people has protected unvaccinated people too which is referred to as herd immunity.
Measles is highly contagious one infected person can spread the virus to 18 other people. Not only can it be fatal, but it can cause lifelong disability in the form of blindness, deafness or intellectual disability.
Over 50 years, vaccines have prevented nearly 94 million deaths from measles and saved 5.7 billion years of life. However there remain challenges in getting measles vaccines out to all those who need them according to WHO, 22 million children missed their routine first dose of measles vaccine in 2022, compared to 19 million in 2019.
The majority of lives saved are in children younger than five years old. More than 9 billion years of life have been saved since 1974.
Young children are the most vulnerable to many of the diseases that can be prevented by vaccines. Many of the diseases prevented by the EPI, such as rubella, polio, pertussis, pneumococcal disease and rotavirus, disproportionately affect young children.
The benefits to older adults are greatest in African and Eastern Mediterranean regions, however people worldwide are still seeing the benefits of vaccination even at age 50.
Vaccination doesn't just save lives, it also prevents the long-term consequences associated with severe disease, especially polio.
For every life saved, 66 years of full health were gained on average, translating to 10.2 billion years of full health gained. This takes into account years of disability caused by disease.
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LHNVD-105, a universal influenza vaccine, shows strong immunogenicity at low doses in pigs, validating previous studies in rodents
Monoclonal antibodies generated by LHNVD-105 demonstrates the need for targeting multiple different conserved regions on the influenza virus
LHNVD-301, a monoclonal antibody cocktail targeting the heat shock protein, demonstrates strong activity against clinical tuberculosis isolates
BETHESDA, Md. & GAITHERSBURG, Md., April 27, 2024--(BUSINESS WIRE)--Longhorn Vaccines and Diagnostics, a One Health company developing vaccines and diagnostic tools for global public health and zoonosis concerns, presented positive data from three key studies of its infectious disease franchise at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2024. ECCMID is taking place online and in-person in Barcelona, Spain from April 27-30, 2024.
Longhorns vaccine and antibody product candidates focus on rapidly mutating viruses that include influenza, coronavirus, and antimicrobial resistant pathogens. The candidates presented include LHNVD-105, an adjuvanted composite peptide vaccine that targets multiple stages of the viral replication process, and a monoclonal antibody cocktail that targets a protein that may play a significant role in allowing tuberculosis to remain in a latent stage.
Influenza is a prevalent zoonotic respiratory virus, with pigs acting as a middleman for generating new virus strains transferrable to humans, birds, and other swine with pandemic potential. This poses a major public health issue and challenges to the swine industry. The first of two studies on LHNVD-105, Longhorns universal influenza vaccine, showcased how unconjugated multi-epitope peptides, formulated with AddaVaxTM adjuvant, generated antibodies that were broadly reactive across multiple influenza virus strains when administered to pigs at low doses. Results included:
Pigs immunized with LHNVD-105 generated IgG antibodies that bound to multiple strains of influenza virus 21 days post primary immunization after a single dose.
Pigs receiving low vaccine doses (1 and 5g) generated binding antibodies to influenza viruses equal to or higher than pigs in the high dose groups (50 and 100g).
No adverse reactions to the vaccine were observed.
"We are very excited to present the first data from our universal influenza vaccine in pigs," said Jeff Fischer, President Longhorn Vaccines and Diagnostics. "Pigs are an ideal model for influenza and the results mirrored the significant rodent data that has been previously published."
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Seasonal circulation of rapidly evolving influenza strains are potential threats in human populations. For individuals with increased risk of exposure to influenza or immunocompromised, new strains resistant to antiviral therapies pose a life-threatening risk. The second study on LHNVD-105 evaluated the binding and functional capabilities of four different isotype-specific anti-influenza mAbs in mice to determine their candidacy for a cocktail therapy approach to influenza. Results demonstrated:
Anti-influenza mAbs LD9 (IgG1, anti-HA), NB5 (IgG2a, anti-NA), GA4 (IgG1, anti-Matrix), and CG6, (IgG3, anti-Matrix) bound equally well to H3N2, but differentially to other contemporary and pandemic strains.
Anti-HA mAb LD9 and anti-Matrix mAb GA4 (both IgG1) preferentially bound to pandemic H5N1 influenza strain, while anti-Matrix mAb CG6 was more reactive with influenza B.
Anti-NA mAb NB5 and anti-Matrix mAb CG6 both had higher affinities to H3N2 and influenza B, but reacted less well to H1N1 and H5N1.
Neutralizing activity of all four mAbs was demonstrated against H1N1 and H3N2.
"Tuberculosis is one of the most common and deadly diseases in the World. Up to one third of the Worlds population has been infected with the bacterium Mycobacterium tuberculosis but does not have active disease," said Gerald W. Fischer, MD, CEO of Longhorn Vaccines and Diagnostics. "The heat shock protein may play a significant role in shielding the bacterium from the immune system and allowing it to survive. The data being presented suggests that both our heat shock protein vaccine candidate and monoclonal antibody cocktail could play a significant role in preventing and treating multi-drug resistant tuberculosis infections."
Mycobacterium tuberculosis (MTB) is a virus that is becoming increasingly resistant to antibiotics and a key pathogen contributing to antimicrobial resistance worldwide. The third study, conducted by the University of Pretoria, explored Longhorns monoclonal antibodies for the prevention and treatment of infections caused by MTB and gram-positive bacteria. The study analyzed the binding capabilities of IgG2a (anti- heat shock protein (HSP16.3)) and IgG2b (anti- Peptidoglycan (PGN)) mAbs to clinical MTB isolates. Results found:
Both IgG2a and IgG2b mAbs demonstrated good binding activity to live and ethanol-killed MTB, and to mid-logarithmic and stationary phase MTB.
The mAbs demonstrated good binding to live clinical MTB isolates at concentrations as low as 0.25 g/mL.
For more information about Longhorn, visit www.LHNVD.com.
About Longhorn Vaccines and Diagnostics
Longhorn Vaccines and Diagnostics is a closely held One Health company based in Maryland that is developing broad coverage vaccines and diagnostic tools for worldwide public health concerns and to prevent future pandemics. Since its inception in 2006, Longhorn has focused on developing broad coverage vaccines and diagnostic tools that can impact a pandemic on a global scale and at all socio-economic levels. Since pandemics flow between humans and animals, Longhorn products play a significant role to surveil, diagnose, prevent and treat the next infectious disease.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240427410246/en/
Contacts
Longhorn Vaccines and Diagnostics LLC Jeffrey Fischer Email: jeff@lhnvd.com
Media Alexis Feinberg ICR Westwicke PR Email: alexis.feinberg@westwicke.com
Investor Relations Stephanie Carrington ICR Westwicke IR Email: stephanie.carrington@westwicke.com
The duration [of the flu season] would be prolonged when there is a transition of the dominating virus strain, the centre said. It is believed that the current influenza season will persist for a period of time and more outbreaks and severe cases might be recorded in the upcoming weeks.
While the city entered the current flu season in early January this year, the extension meant that it would last longer than the average flu period of eight to 12 weeks.
Dr Mike Kwan Yat-wah, an honorary associate professor at the University of Hong Kongs department of paediatrics and adolescent medicine, said a relatively low vaccination rate could give rise to alternating flu strains.
He said about 50 per cent of the citys population had been inoculated with the latest seasonal flu vaccine.
If we need to build an immunity barrier to prevent infections of alternating viruses, an overall vaccination rate would need to reach 70 to 80 per cent to do so, Kwan said.
He added that as the city experienced a peak of H1 infections starting from March last year, the immunity against the virus subtype would decline roughly six months later, suggesting that people could also be more susceptible to the strain.
When the populations immunity is low, the flu season could be longer we could see a majority of people getting infected before the transmission stops, he said.
Kwan added there was no significant difference in terms of transmissibility or virulence between H1 and H3.
Hong Kong, global experts to work on longer-lasting flu vaccines, Post learns
Professor Ivan Hung Fan-ngai, an infectious disease expert from the same university, pointed out it was quite common to have two different flu virus strains in one season, especially when community immunity was low after Covid-19.
He said the low immunity was caused by a lack of thorough flu infections in the community during Covid-19 pandemic, together with the low flu vaccination rate.
Health authorities said Hong Kong underwent a 16-week winter flu season in 2015-16 after the dominance of flu A virus was overtaken by flu B later.
The six-year-old girl died this week after having contracted the H1 subtype virus and developing encephalopathy, also known as altered brain function.
The girl had a history of good health and had received a flu vaccine for this season, authorities said.
The news came just five days after the announcement of the death of an unvaccinated eight-year-old girl, who had also caught the H1 strain.
Girl, 6, in critical condition after contracting flu in Hong Kong
Kwan explained that a person could still develop complications following a flu jab under certain conditions, such as undiagnosed congenital immunodeficiency or metabolic disorders, a severe flu infection or another bacterial infection.
Health authorities said there had already been a significant increase in the number of flu-like outbreaks at schools and institutions in the week ending April 20 compared with the first week of the month, rising from 10 to 29.
The [centre] appealed again to members of the public to heighten their vigilance, and people belonging to high-risk priority groups should receive seasonal influenza vaccination as soon as possible for prevention of severe disease and death.
