When a new RSV vaccine for pregnant people arrived last fall, Sarah Turner, a family-medicine physician at Lutheran Hospital, in Indiana, couldnt help but expect some pushback. At most, about half of her eligible pregnant patients opt to get a flu vaccine, she told me, and very few agree to the COVID shot.
But to Turners surprise, patients clamored for the RSV shotsome opting in even more eagerly than they did for Tdap, which protects newborns against pertussis and had previously been her easiest sell. For once, expectant parents were the ones starting conversations about immunizations.
Each year in the U.S., respiratory syncytial virus hospitalizes an estimated 58,000 to 80,000 kids under the age of 5; the risks are highest for infants, for whom the virus is enemy No. 1, says Sallie Permar, an immunologist and pediatrician in chief at NewYork-Presbyterian/Weill Cornell Medical Center. But this past season marked the first time that the U.S. had two tools that could substantially shrink that toll: a vaccine for pregnant people, who can then pass antibodies to their child, and a monoclonal antibody, known as nirsevimab, that is given directly to infants. Their arrival feels akin to the end of polio, Anne-Marie Rick, a pediatrician and clinical researcher at Childrens Hospital of Pittsburgh, told me: With both shots in widespread use, the risks of winter illness could forever look different for the youngest Americans.
But some experts worry that these powerful shots are being squandered. The CDCs seasonal recommendations governing their use may simply be too strict, Permar told me. In keeping with those guidelines, many practices stopped giving the maternal vaccine at the end of January; the main window for administering the monoclonal antibody is expected to close at the end of this week. The next eligibility windows wont open for months. The U.S has two brand-new shots that protect extraordinarily well against a deadly respiratory virusand that people actually want to takeand it is holding them back.
The guiding principle behind the CDCs recommendations has logic to it. RSV is a seasonal virus, and both injections are thought to offer protection for about six months. For the maternal vaccine, which is administered between 32 and 36 weeks of pregnancy, the clock on the babys protection starts after birth. So if a pregnant person gets the vaccine in Juneoutside of the CDCs recommended windowand has their baby in July, their child may be vulnerable again come February, before RSV season typically ends. In theory, spring and summer infants might be better protected by getting nirsevimab starting in October, when RSV usually arrives. Current guidelines also require a choice between the two options: Most infants that benefit from maternal vaccination are not eligible to also receive nirsevimab.
Read: The worst pediatric-care crisis in decades
This past season, though, nirsevimab was in severely short supplyin large part because drug companies seem to have underestimated demand, William J. Muller, a pediatric-infectious-disease expert at Northwestern who helped trial the monoclonal antibody, told me. Many hospital systems also balked at the cost of the new drug, which is pricier than the maternal vaccine, wasnt yet bundled into the expense of delivering infants, and wasnt consistently covered by insurance. The shortfalls became so dire that Sanofi, nirsevimabs manufacturer, stopped taking new orders for certain doses of the monoclonal antibody as early as October. The CDC issued a health alert, calling on providers to restrict administration of those doses to only the highest-risk infants. In our hospital system, we had some for the NICU babies, and that was literally it, Turner, of Lutheran Hospital, told me.
Nirsevimab should be more available this year: Spokespeople from AstraZeneca and Sanofi told me that the companies are confident we will meet the global demand for the antibody in 2024. But last year set quite a low bar. And when the window for administration opens in Octoberpotentially already coinciding with RSVs risesupplies could go fast, as parents who havent been able to get shots for themselves or their babies rush to catch up, Grace Lee, a pediatrician at Stanford, who advised the CDC on its RSV guidance, told me. (The CDC did not respond to a request for comment.) Opening the administration window earlier for either the vaccine or the monoclonal antibody could ease that burden: The U.S. starts immunizing people against the flu well ahead of the seasons start, Lee said, because its just not feasible to vaccinate the entire U.S. population in a week.
For several years, too, RSV has been on the move, Permar told me, thanks in large part to pandemic mitigations. The virus was virtually absent in 2020, only to come roaring back for a bizarrely early season that began during the summer of 2021 and had mostly concluded by the end of January 2022. In the past two seasons, the virus has also arrived somewhat early, starting with a September rise. If that pattern holds, waiting until September to vaccinate pregnant people or until October to immunize infants might leave many newborns more vulnerable than they need to be for weeks or months.
Many experts do anticipate that RSVs pattern will quickly settle back to its norm. Over the decades, its consistency has been remarkable, says Sarah Long, a pediatrician at Drexel University who advised the CDC on its guidelines for both new RSV interventions. But even in more predictable years, RSV transmission varies across regionssometimes kick-starting during the summer in the South and lingering until spring further north. The recommendations cant be a one-size-fits-all across the U.S., says Shabir Madhi, a vaccinologist at the University of the Witwatersrand, in South Africa, who helped lead clinical trials of the maternal vaccine. These are judgment calls: France opens its nirsevimab window earlier than the U.S.; Belgium will allow some pregnant people to receive a vaccine as early as the spring. The U.K. is weighing whether to offer both injections at any time of year.
One argument for the current seasonal window is that giving a vaccine or a monoclonal antibody injection too early might mean recipients miss out on protection at the end of the season, Karen Acker, a pediatrician at Weill Cornell, told me. But Permar and others are hopeful that the effects of the new RSV interventions might last longer than five or six months, which is about when clinical trials stopped directly testing their effects. Early data for nirsevimab, for instance, suggests that a little bit of protection may even trickle into subsequent seasons, Muller told me.
Read: Falls vaccination routine didnt have to be this hard
RSV is also of greatest threat to children within the first few months of life, when their respiratory tracts are still tiny and developing. Given the choice between offering the maternal vaccine a little earlywhich could leave an older infant a bit more vulnerable at the seasons endand waiting to administer nirsevimab to a young infant after RSV season has started, the former might actually be the safer strategy. Plus, summer babies who dont get nirsevimab at the hospital are less likely to get it later, especially if their parents arent regularly taking them to see a pediatrician. Giving a shot on the early side is better than never giving one all, Joshua Salomon, a health-policy researcher at Stanford, told me.
In theory, the CDCs guidelines do make room for adjustments in administration windows, in accordance with local RSV trends. But those decisions can be difficult to execute when providers have to place orders ahead of time and store vials in limited space. So far, many doctors offices and hospitals have stuck to the months outlined by the CDC guidance. The cutoff dates have been taken very dogmatically, Rick told me. At the start of the past season, infants just one day over the recommended dosing age of eight months or younger were denied nirsevimab, Turner told me. Then, a lot of providers simply stopped offering the maternal vaccine after January 31, or simply ran out.
When both the need and the enthusiasm for a vaccine or drug is strong, taking every opportunity for protection makes sense. Several experts I talked with supported wider windows; Permar thinks the U.S. should even consider offering the maternal vaccine year-round. To her mind, restrictions regarding both seasonality and gestational age too strongly limit the chances that a baby will be protected. Some providers also noted that, given all the uncertainties, they would recommend the maternal vaccine as primary defense, leaving nirsevimab as the backupsimply because the vaccine can be delivered first. A maternal shot can set babies up with protection from the moment of birth, a sort of insurance policy that can guard against nirsevimab supply or delivery issues. A wider window of vaccine eligibility might not be a perfect solution. But it could get more infants protected when they most need itputting to best use a shot that people are actually willing to get.
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This week, I wrote about anti-vaccine messages in political discourse, prompting many readers to ask how they should respond if a family member or friend expresses skepticism toward routine childhood immunizations.
I spoke with Sean OLeary, a specialist of pediatric infectious diseases and a professor at the University of Colorado, whose expertise is vaccines and vaccine communication. He told me that when he has conversations with parents who are hesitant about immunizations, he keeps in mind that they are just trying to figure out what is best for their kids.
A similar approach could help people who arent medical professionals who want to help loved ones. Heres how to respond to 10 common vaccine concerns.
I dont need to vaccinate my kids because the chance of contracting the disease is so low.
As OLeary explained, The chance of getting the disease is so low because we vaccinate. Many diseases have been eliminated because of vaccinations, but this wont last if population immunity goes down. Not vaccinating could put your child and others around them at risk.
Natural immunity is better than immunity from vaccination.
This is just simply incorrect, OLeary said, because the diseases themselves are so severe and the vaccines are incredibly safe.
He shares with parents that when he began training in the late 90s, he treated many kids who had to be hospitalized for rotavirus, a then-common gastrointestinal ailment. Most were fine after hydration, but some children died from it. Since the rotavirus vaccine was widely adopted, he hardly ever sees kids hospitalized with this disease. Another vaccine introduced in recent decades is the pneumococcal conjugate vaccine, which has substantially decreased rates of pneumonia and meningitis in kids.
Vaccines dont go through the rigorous testing of other medicines.
This is wrong. In fact, vaccines are held to a much higher safety standard than other medicines because they are used to prevent rather than treat disease.
When we treat diseases, well tolerate some side effects, OLeary told me. Someone who has heart disease or diabetes will accept some side effects if it helps control their illness. But with vaccines, because they are used in healthy people who do not have the illness, there are even more stringent safety standards.
Vaccines must go through multiple levels of approval by the Food and Drug Administration and Centers for Disease Control and Prevention, and they are also subject to a robust safety surveillance system to detect rare side effects. Routine childhood immunizations have been around for decades, and millions of children in the United States and globally have safely received them.
I dont trust the FDA or CDC.
OLeary, of course, trusts federal health officials, but he recognizes that some people might not. In those cases, he advises them to consult resources such as their local childrens hospital and university or to speak with their pediatrician or family doctor.
I dont trust science.
This is tough, OLeary concedes. One possible approach he suggests is to ask whether they take any medicine or use electronics such as a smartphone.
The phone in your hand is built on decades of science, he said. It doesnt make a lot of sense to treat vaccines differently from other scientific developments.
Vaccines could cause autism.
Thats a very unfortunate example of something that has no basis in science, OLeary told me. That myth has been disproven many, many times, yet it still persists.
With some families, OLeary finds it helpful to go into the details of how the myth started a 1998 paper spearheaded by a man named Andrew Wakefield. But that study was retracted because of serious scientific flaws. Wakefield was subsequently exposed for deliberately perpetuating disinformation for financial gain. Crucially, many other studies have since proved that there is no association between immunizations and autism.
Someone I know has a child who developed [negative consequence].
A personal anecdote that elicits an emotional response can be hard to respond to. The thing we try to point out is that association does not equal causation, OLeary said. Just because something happened after something else doesnt mean it was causative. It can help to bring up again the safety surveillance systems that rigorously evaluates reports of possible associations.
My child had a bad reaction with another vaccine, so Im holding off on more.
Just because your child had a reaction to one vaccine doesnt mean they will have the same to another. OLeary also assures parents that more pronounced side effects such as fever or soreness at the injection site are signs that the immune system is responding appropriately. That means if their child encounters the disease in the future, they will have immunity to it.
Im not saying no to vaccines forever, just delaying them until my child is older and more robust.
Most diseases that we vaccinate for are most severe for the youngest children. Thats why the vaccine schedule starts in infancy. By waiting, OLeary tells parents, you are leaving your children at risk for infections at the time of their highest risk.
Vaccines are against my religion.
There really arent organized religions of any size that object to vaccination, OLeary explained. In fact, many urge vaccinations as part of adherents duties to safeguard those around them, especially the most vulnerable.
As loud as some anti-vaccine voices can be, they are a tiny minority. Less than 1 percent of kids in the United States are completely unvaccinated, OLeary said. Of these, a substantial proportion come from families that havent eschewed immunizations but lack access to medical care.
That means the vast majority of parents are choosing to vaccinate their children. Many of those folks feel pretty strongly, and we dont hear from them enough, he said.
OLeary urges those who feel passionate about vaccines to get involved with their local immunization coalition. Other advocacy venues include Voices for Vaccines and Immunize.org. Its not only health-care providers who can share their expertise; everyone can explain why they decided to vaccinate their kids and why vaccines protect us and everyone around us.
Muddy Paws Second Chance Rescue sponsored a vaccine clinic for dogs and all the shots were free.The rescue offered dog owners free distemper parvo vaccines and free will donation Bordetella shots.It also offered people the chance to get their dogs micro-chipped for only $15, including the registration of the chip for life.Muddy Paws said it provides the records and if you come to the clinic, it's no questions asked."We're really trying to get it out there, especially for the people who can't afford it or if it's the choice of vaccinating their dog or paying their light bill. We want to be here to help them. Giving up your dogs when they're sick is probably the most heartbreaking thing you can do. And if we can help prevent that, to help prevent the spread in the community. Well, absolutely. Keep doing this and running our tushies off," said Heather Reese of Muddy Paws.Muddy Paws said they typically average about 100 dogs every clinic and plan on hosting a clinic every month.Click here for the latest headlines from KETV NewsWatch 7
Muddy Paws Second Chance Rescue sponsored a vaccine clinic for dogs and all the shots were free.
The rescue offered dog owners free distemper parvo vaccines and free will donation Bordetella shots.
It also offered people the chance to get their dogs micro-chipped for only $15, including the registration of the chip for life.
Muddy Paws said it provides the records and if you come to the clinic, it's no questions asked.
"We're really trying to get it out there, especially for the people who can't afford it or if it's the choice of vaccinating their dog or paying their light bill. We want to be here to help them. Giving up your dogs when they're sick is probably the most heartbreaking thing you can do. And if we can help prevent that, to help prevent the spread in the community. Well, absolutely. Keep doing this and running our tushies off," said Heather Reese of Muddy Paws.
Muddy Paws said they typically average about 100 dogs every clinic and plan on hosting a clinic every month.
Click here for the latest headlines from KETV NewsWatch 7
Craig L. Slingluff Jr., MD, and his team have developed a second-generation melanoma vaccine to treat the dangerous skin cancer.
A second-generation melanoma vaccine developed at UVA Cancer Center improves long-term survival for melanoma patients compared with the first-generation vaccine, new research shows. Interestingly, the benefit of the second-generation vaccine was greater for male patients than female patients. That finding could have important implications for other cancer vaccines, the researchers say.
The vaccine developers, led byCraig L. Slingluff Jr., MD, found that they could enhance the effectiveness of their melanoma vaccine by simultaneously stimulating important immune cells known as helper T cells to recognize melanoma proteins, in addition to stimulating killer T cells against melanoma. This boosted patient survival and helped prevent reoccurrences of the cancer.
The researchers are not sure why the approach was more effective in men, but biologic sex is emerging as an important factor in outcomes of patients with melanoma, in particular with immune therapies. The findings support the importance of understanding how best to benefit women and well as men with effective immunotherapies.
These findings support the promise of this second-generation melanoma vaccine for prolonging survival of patients after surgery for high-risk melanoma, said Slingluff, a surgical oncologist and translational immunologist at UVA Health and the University of Virginia School of Medicine. We hope that we can make this available to patients in addition to other effective immune therapies so that they may have even greater benefit than either treatment alone.
People commonly think of vaccines as something you take to avoid getting sick from viruses. Most cancers do not have a known viral cause, but melanoma vaccines can induce immune responses against human melanoma cells, and Slingluff and others have been working to make them effective for treatment of melanoma. (There are cancers that are caused by viruses, and some vaccines against those viruses have been very effective at preventing cancers they cause for example, there are vaccines against human papillomavirus and hepatitis B).
Slingluffs melanoma vaccine targets a form of skin cancer that kills thousands of Americans every year. In seeking to make the vaccine more effective, he and his team tested two different approaches to stimulating both CD4+ helper T cells and CD8+ killer T cells in patients with high-risk melanoma. More than 160 clinical trial volunteers were given, at random, one of two vaccine preparations of purified peptides to stimulate their helper T cells.
Fifteen years after the last participant was enrolled in the trial, overall survival rates were encouraging with both vaccine approaches, but overall survival was better for those with the second-generation vaccine. Those who benefitted most appeared to be younger men with earlier-stage melanoma. The researchers characterize the benefit as meaningful and durable in a new scientific paper outlining their findings.
We were very excited by these findings and for the promise to improve survival with these vaccines, Slingluff said. Combination of the second-generation vaccine with other immune therapies may further increase the benefit for patients.
The multicenter trials findings suggest that both age and sex may play important roles in determining immune therapy outcomes. That is important information for doctors and researchers developing these treatments, Slingluff says.
The differences in benefit based on age and biologic sex highlight the need to understand reasons for those differences so that we can provide the same benefit for all patients, Slingluff said. We are excited to build on these exciting findings.
Slingluffs pioneering research is part of UVA Cancer Centers ongoing mission to develop new ways to treat cancer and improve patients cancer treatment options. In recognition of those efforts, the National Cancer Center has named UVA Cancer Center one of only 56 comprehensive cancer centers in the country.The designationrecognizes elite cancer centers with the most outstanding patient care and research programs in the nation.
Advancing the field of immunotherapy is also a key pillar of UVAs upcomingPaul and Diane Manning Institute of Biotechnology, now under construction at Fontaine Research Park. The institute is poised to fast track the development of new treatments and cures and transform how healthcare is delivered across the state and beyond.
Slingluff and his team havepublished their findings in the scientific journal Nature Communications. In addition to Slingluff, the multi-institutional team included Emily K. Ninmer, Hong Zhu, Kimberly A. Chianese-Bullock, Margaret von Mehren, Naomi B. Haas, Merrick I. Ross and Lynn T. Dengel.
The research was supported by theNational Cancer Institute, grants R01CA118386 and P30CA044579; gifts from Alice and Bill Goodwin; and the Commonwealth Foundation for Cancer Research.
Slingluff disclosed that he receives licensing fees for patents for peptides used in cancer vaccines; his work has been supported by Celldex, Glaxo-Smith Kline, Merck, 3M and other companies. A full list of the authors disclosures is included in the paper.
To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog.
CHARLESTON, W.Va. (AP) Republican Gov. Jim Justice on Wednesday broke with West Virginias GOP-majority Legislature to veto a bill that would have loosened one of the countrys strictest school vaccination policies.
West Virginia is only one of a handful of states in the U.S. that offers only medical exemptions to vaccine requirements. The bill would have allowed some students who dont attend traditional public institutions or participate in group extracurriculars like sports to be exempt from vaccinations typically required for children starting day care or school.
Our kids are our future, Justice said in a letter explaining the veto. They are our most important resource, and I will protect them with everything I have.
The governor said West Virginia is way ahead of the pack in protecting children from preventable diseases like measles because of its school vaccine policy. He said he had to defer to the licensed medical professionals who overwhelmingly spoke out in opposition to the legislation.
I hear how strongly people believe in one side or the other on this subject, and I respect all opinions, he said. But I must follow the guidance of our medical experts on this subject.
Justice, who is running for Democrat U.S. Sen. Joe Manchins seat, received immense pressure to reject the bill from health care leaders, educators and parents. He refused to answer whether or not he planned to sign it before Wednesdays veto, saying he needed time to think through the decision.
The veto came on the last day before a key deadline that would have allowed the bill to go into law without Justices signature.
The bill, which received majority support in both legislative chambers even with an overwhelming lack of support from health care leaders, would have exempted private and parochial schools from state law and allowed them to develop and enforce their own policies on vaccinations. Virtual-only public school students would also have been exempt.
All students participating in West Virginia school activities that result in competition, including but not limited to sports, would still have needed to be vaccinated.
The bill was publicly opposed by the head of the states two teachers unions, the West Virginia Hospital Association and the West Virginia Medical Association, among other organizations.
Dr. Clay Marsh, West Virginia Universitys vice president and executive dean for health sciences, also urged Justice to vote against the bill. As COVID-19 Czar for the State of West Virginia, Marsh was tapped as a trusted advisor when it came to preventing spread of the virus in the state.
Justice was hailed by state health care leaders for his pro-vaccine stance during the coronavirus pandemic. When the COVID-19 vaccine was developed, Justice was among the first top elected officials in the country to receive a shot, even livestreaming the inoculation on social media.
Before Justice vetoed the bill, Kanawha-Charleston Health Officer Dr. Steven Eshenaur said he was deeply worried about the consequences that could come from the legislation being made law.
Yes, personal freedom is vital to our way of life in West Virginia and America, and I am all for it, he said in a statement. But not when the lives of children are in danger.
Eshenaur said state leaders owe it to children to keep them safe, healthy and free of disability if its in their power to do so.
Hear this on repeat: If you are anti-vaccination, you are pro-disease. Its as simple as that, he said.
West Virginia law requires children to receive vaccines for chickenpox, hepatitis-b, measles, meningitis, mumps, diphtheria, polio, rubella, tetanus and whooping cough, unless they receive a medical exemption. West Virginia does not require COVID-19 vaccinations.
Health care leaders say other states have used West Virginias immunization requirements as a model to strengthen their immunization requirements after experiencing measles outbreaks. West Virginia, along with California, Connecticut, Maine and New York, are the only states without nonmedical vaccination requirements.
But a growing number of parents in the state have expressed frustration with the states policy and say they should have the freedom to make their own decisions about their childrens vaccination status.
West Virginia University School of Medicine Professor Dr. Alvin Moss was one of a handful of doctors supportive of the bill, arguing before the Senate Health Committee that the states current compulsory vaccination policy is medically unethical because it doesnt allow informed consent.
In 2017, the anti-vaccine requirement group West Virginians for Health Freedom had 300 families as members. The organization has grown to at least 3,000 members in 2024, Moss said.
The bills original intent, as introduced in the state House of Delegates, was to eliminate vaccine requirements for students in public virtual schools. It was expanded in a House committee to allow private schools to set their own vaccination standards, unless a student participates in sanctioned athletics.
The bill also created a religious exemption for any child whose parents or guardians present a letter stating the child cannot be vaccinated for religious reasons. That was taken out in the Senate.
Stall experiments at COVAB in 2017.
COVAB/Makerere University
In Uganda, researchers are working towards field trials of a vaccine that aims to use proteins from disease-bearing ticks to protect cattle and reduce pesticide use.
Uganda is estimated to suffer an direct and indirect costs of over$1 billion a year from the impacts of ticks and tick-borne diseases, according to a 2021 review, threatening the countrys dairy sector, the second biggest foreign exchange earner after coffee.
Margaret Saimo-Kahwa, senior Lecturer at the College of Veterinary Medicine, Animal Resources and Biosecurity at Uganda's Makerere University says that diseases from ticks, such as East Coast Fever, Babesiosis, Anaplasmosis and Heartwater cause of high death rates in cattle, leading to higher food insecurity in Africa.
"Im researching the use of recombinant tick gut proteins identified from local ticks in Uganda, as a way of creating an anti-tick vaccine," she says adding that the hope is to protect cattle while reducing the use of acaricides (pesticides).
"The vaccine couldnt have come at a better time, when Uganda is grappling with acaricide resistant ticks, exacerbating tick-borne diseases," Saimo-Kahwa says, adding that today, the only practical preventative solution to East Coast Fever, has been the unconventional "infection and treatment method" developed in the 1970s.
Although anti-tick vaccines have been produced at scale in Australia, Cuba, Mexico, and Latin America for the past two decades, roll-out in sub-Saharan Africa has been hindered by their lack of efficacy against tick strains native to the region.
She explains that the genetic sequences of the tick gut protein variants (Ra92A and Ra85A) were synthesized into a yeast host: Pichia pastoris and the team has already built the technological capacity to produce these proteins and formulate them into a patent-pending candidate vaccine at a newly upgraded production facility.
"Once we mass produce these batches from our specialized vaccine line, we aim to test them in the field to access their immunogenicity, safety and efficacy in large numbers of cattle against all important tick species from the different geographical regions of Uganda," Saimo-Kahwa says, "Once we have achieved this, we will have developed locally in Uganda a conventional anti-tick vaccine ready not just for commercial up-scaling, but one which has cross-species protection against other tick infestations, on top of developing cGMP compliant vaccine production capacity, a first in Uganda and Africa."
R. appendiculatus ticks which are found in Uganda
getty
Saimo-Kahwa grew up in the small Budaka district in eastern Uganda,
After going through the Ugandan school system, she graduated with a bachelor of Veterinary Medicine at Makerere University in Kampala, Uganda and a master's degree in Applied Immunology at Brunel University in London, UK.
"It wasnt until 2005 when I received funding for a sandwich program at Makerere University and Wageningen University, the Netherlands, that I embarked on a PhD at Makerere University with interest in tick proteins with potential for candidate vaccines took shape," Saimo-Kahwa says, adding that during her PhD work, she investigated the potential of tick gut and salivary gland proteins for use in an anti-tick vaccine; and realized that Uganda might be in urgent need of an anti-tick vaccine.
Saimo-Kahwa explains that scientists from the Global South bring knowledge of the local conditions, problems, and solutions to solving a problem inherent to sub-Saharan African landscapes.
"I believe the need for Global South scientists who can solve the regions own health issues has never been more pressing, a fact never more evident than during the COVID-19 pandemic," she says, "I believe many African countries, including Uganda learnt the lessons from that period; Uganda is for instance doubling down on building domestic capacity not just in vaccine development and production, but in science-led national transformation."
Lab-growing culture in 2019.
COVAB, Makerere University
Meanwhile, the hunt for vaccines to a different disease spread by beasts of burden in the Global South is underway.
Amanda Elyssa Ruiz, a PhD student at Brown University in the United States and a Howard Hughes Medical Institute (HHMI) Gilliam Fellow, is looking for potential vaccines to protect against schistosomiasis, a disease that impacts over 250 million people every year, making it the second most socio-economically devastating parasitic disease after malaria.
In countries where schistosomiasis is found, water buffalo are the key labor force for wetland rice agriculture, as well as the main way that humans get infected, so finding a vaccine that protects both would be a big step forward.
"My main project is to identify novel vaccine candidates for schistosomiasis using epidemiologic data alongside immunologic and biochemical approaches," she says, "The Kurtis lab has developed a screening strategy for vaccine candidates which identifies the antigens on the parasite, Schistosoma japonicum."
I'm an Australian science journalist based in Cali, Colombia covering STEM in The Global South. I'm the current Vice-President of the Colombian Association of Science Journalism (ACPC) and helped organize the 12th World Conference of Science Journalists, with 600+ attendees in Medellin, Colombia.
Genome extraction of AP33, AP65, and -actinin proteins
The sequences of AP33 (accession number: Q65ZG5), AP65 (accession number: Q27093), and -actinin (accession number: O96524) proteins were extracted from the UniProtKB database.
Prediction of B cell epitopes for all three proteins, AP33, AP65, and -actinin, was done using Bepipred and IEDB servers (Kolaskar and Tongaonkar) (Additional file 1: Table S1).
IEDB and Rankpep databases were also used to predict T cell epitopes. The allelic group for MHCII alleles DRB1*0101, *0301, *0401, *0701, *0801, *1101, *1301, *1501, which covers the genetic background of most humans, was selected. The most important epitopes with the highest score were selected (Additional file 2: Table S2).
The regions of AP33, AP65, and -actinin proteins with the highest epitope abundance are considered as the target domain for vaccine design to select the domains that make up the vaccine candidate. Finally, nine epitope-rich domains from these three proteins were selected as vaccine candidates, which contain a large number of B cell and T cell epitopes (Table1).
By combining selected epitope-rich domains at different positions using EAAAK, EAAAKEAAAK, and GGGGS linkers, several protein constructs were designed. The designed constructs were evaluated based on physicochemical properties, antigenicity, and secondary and tertiary structure, and finally the most suitable construct was introduced as a vaccine candidate (Additional file 3: S3) (Fig.1a, b).
a Schematic diagram of the final construct of the multiepitope protein. b The tertiary structure of the designed protein
Using the EXPASY ProtParam server (http://expasy.org/tools/protparam.html), the physical and chemical properties of the designed structures such as the number of amino acids, molecular weight, PI, number of charged amino acids, amino acid composition, hydrophobicity, and hydrophilicity were obtained. The results of this investigation showed that our designed vaccine candidate protein finally consisted of 780 amino acids and had a molecular weight of 85,190.25daltons (Table2). The instability index (<40) indicates that the designed protein has high stability to induce an immunogenic response. The instability index of our vaccine candidate was 35.8, which classifies the protein as stable. The aliphatic index of the recombinant protein was calculated to be 86.04, indicating the stability of this protein at different temperatures (Table2).
The Vaxijen 2.0 server predicts the designed protein as an antigen with a threshold score0.4 (score: 0.4983). The Evaller web server was used to check the allergenicity of the designed structure. The designed protein was not allergenic. The solubility of the vaccine candidate was also evaluated using the Protein-sol server. Our selected protein has a solubility score of 0.555. Solubility-scaled proteins using the Protein-sol server that have a score greater than 0.45 indicate a higher solubility than the average soluble E.coli protein from the experimental solubility dataset [45]; therefore, our designed protein has a high solubility.
The GOR software was used to check the second structure of the designed structures. The amino acids that make up these recombinant proteins are involved in the formation of random coils, alpha helixes, and beta strands. The results showed that out of 780 amino acids, 430 amino acids (55.13%) are alpha helix, 96 amino acids (12.31%) are extended strands, and 254 amino acids (32.56%) are random coils (Fig.2a). Tertiary structures were predicted by the I-TASSER server for designed protein sequences. All structures were validated and the best structure was selected. Predicted tertiary structures were evaluated using the MolProbity, ProSA-web, and SAVES servers. The MolProbity server was used to evaluate the structural similarity of new proteins to the best-known structures of similar proteins (http://molprobity.biochem.duke.edu/help/validation_options/summary_table_guide.html). On MolProbity analysis, the protein structure analysis was evaluated based on the Clash score and the MolProbity score. The SAVES server (https://saves.mbi.ucla.edu/) was also used to check the Ramachandran plot and evaluate the placement of amino acids in the favored, allowed, and disallowed regions.
Predicting and validating the secondary and tertiary structure of the vaccine candidate. a Secondary structure of the designed protein. b Validation of the tertiary structure of the protein by ProSA-web. c Validation of the tertiary structure of the protein by Ramachandran plot
On MolProbity evaluation, it was found that the Clash score for this protein was 2.49 (99% similar to the structures). Also, the MolProbity score was 2.13 (69% similar to the best structures). ProSA-web analyzed a 3D model of the vaccine candidate using an energy plot and Z-score. ProSA-web analyzed a 3D model of the vaccine candidate using energy plot and Z-score. The Z-score of the selected protein was 3.44, which was within the range of native protein structure (Fig.2b). The evaluation of the Ramachandran diagram also showed that 97.4% of the amino acids were in the favored and allowed region and 2.6% were in the nonallowed areas, indicating the appropriate structure predicted for the protein (Fig.2c).
Ellipro servers were used to predict this type of epitope (Fig.3af). The 3D structure of the designed vaccine protein used in the Ellipro server was predicted by the I-TASSER server. The most antigenic epitopes with a score above 0.5 is presented in Table3.
The most potent vaccine candidate conformational epitopes designed using the Ellipro server. a Epitope with score 0.901, b Epitope with score 0.736, c Epitope with score 0.723, d Epitope with score 0.657, e Epitope with score 0.641, f: Epitope with score 0.596
Cluspro 2.0 was used to study the proteinprotein binding between the designed vaccine candidate with TLR4 and TLR2. To select the best interaction, the parameters of the weighted score and number of clusters calculated by Cluspro 2.0 were evaluated. In addition, hydrogen and hydrophobic bonds between the vaccine candidate and TLR4 and TLR2 were investigated using the LIGPLOT tool. Finally, we considered the lowest energy and the lowest affinity (Kd) obtained from the PRODIGY web server as essential standards for selecting the strongest complexes. The results showed that there is a strong interaction between the vaccine candidate with TLR4 and TLR2 (Table4). Interactions between TLR2 (Fig.4) and TLR4 (Fig.5) and the designed vaccine candidate were observed using PyMOL and LIGPLOT. As shown in Figs.4 and 5, the vaccine candidate made a strong interaction with the active site of the receptors, and this binding includes the essential amino acids Ile319, Phe322, Phe325, Tyr326, Val348, Phe349, and Pro352 for TLR2 and the amino acids Arg434, Arg380, Lys341, Lys263, and Gln339 for TLR4.
a Graphic representation of the interaction of the designed vaccine candidate with the TLR2 complex. b LIGPLOT representation of the amino acids involved in the interaction between the protein vaccine candidate and TLR2. *Hydrogen bonds between receptors (blue) and the protein vaccine candidate (green) and hydrophobic interactions with receptors (black) and the protein vaccine candidate (blue) are indicated by dark green lines
a Graphical representation of the interaction of the designed vaccine candidate with the TLR4 complex. b LIGPLOT representation of the amino acids involved in the interaction between the protein vaccine candidate and TLR4. *Hydrogen bonds between receptors (blue) and the protein vaccine candidate (green) and hydrophobic interactions with receptors (black) and the protein vaccine candidate (blue) are indicated by dark green lines
To verify the stability of the designed protein structure and proteinreceptor complexes, MD simulation was performed for up to 100ns. The RMSD parameter is used when analyzing the results of MD simulations of proteins and complexes to obtain the degree of movement of the protein or atoms when the ligand is placed in the active site of the receptor and to evaluate the stability of the structure, deviation, and conformations of the protein or complex during the simulation period. A lower RMSD value indicates more stability and less fluctuations during the simulation. The analysis of the results related to the RMSD of the designed protein and the complexes showed that the designed protein reached stability after about 10ns and its average RMSD was 0.95nm (Fig.6a). This stability is maintained during the simulation up to 100ns. Also, proteinTLR2 complexes with an average of 1.7nm are stable during the simulation (Fig.6a). The proteinTLR4 complex reached stability after about 40ns with an average RMSD of 1.1nm, and considering that the fluctuations during 40100ns are less than 0.3nm, it can be concluded that the complex has reached stability (Fig.6a). Another parameter that has been investigated in the evaluation of MD simulations is the Rg, which is evaluated the amount of compression changes during the MD simulation. Rg is defined as the distribution of a proteins atoms around its axis and is widely used in the calculation of protein behavior. Therefore, this variable allows us to analyze the overall dimensions of the protein, and the more stable the compression of the protein is during the simulation, it indicates the stability of the protein and the complexes. As the graph shows, the fluctuations of the designed protein alone and in interaction with TLR4 and TLR2 are stable during the simulation (Fig.6b).
a RMSD results of the designed protein and proteinTLR2 and proteinTLR4 complexes in unit time (ns). b Rg results of the designed protein and proteinTLR2 and proteinTLR4 complexes per unit time. c RMSF results of the designed protein in the noninteracting form and in the interacting form with TLR2 and TLR4
The RMSF of the amino acid residues can be used to evaluate the motion and flexibility of the structure. In addition, we decided to perform an RMSF analysis to examine the changes in the backbone atoms of the designed protein and the proteinTLR4 and proteinTLR2 complexes. In this analysis, the average value of changes of each residue during the simulation was plotted. As shown in Fig.6c, the RMSF values show small fluctuations (less than 0.3nm) for most amino acids in proteinTLR4 and proteinTLR2 complexes compared with the designed protein. These results show that the designed protein becomes more stable in interaction with the immune system receptors.
Snapshots taken at 0, 50, 75, and 100ns intervals to check the state of the vaccine during the simulation showed that the structure of the vaccine and the site of interaction of the vaccine with the receptors were stable during the simulation (Fig.7ac).
Snapshots of 0, 50, 75, and 100ns of MD simulation of the vaccine candidate and ligandreceptor complexes. a The vaccine candidate, b vaccine candidateTLR2, and c vaccine candidateTLR4 complexes. Brown: 0ns; blue: 50ns; purple: 75ns; light green: 100ns
Using covariance matrices of C atoms, PCA calculates the significant motions of atom pairs associated with vital biological functions. The first two principal components (PC1 and PC2) of the candidate vaccine, candidate vaccineTLR2 and candidate vaccineTLR4 complexes were generated by projecting the trajectories onto their respective eigenvectors. Figure8 shows the PCA of the three structures. The plot shows that most of the common essential subspace was occupied by the vaccine candidateTLR2 and vaccine candidateTLR4 complexes. In the Eigenvector (EV) plots, the three structures shared a common conformational subspace. The sampling of both systems demonstrates the stability of the complexes and the vaccine candidate in the simulation. In addition, the FELs of the first and second PCA showed that the vaccine candidate, vaccine candidateTLR2 and vaccine candidateTLR4 complexes had global energy minima of 7.71, 7.54, and 7.15kJmol1, respectively (Fig.9). The Gibbs energy landscape shows the same energy range for all three structures and it can be argued that the structures have not undergone sudden drastic changes and are stable. These results are consistent with the analysis of RMSD, Rg, and RMSF values.
Conformational sampling in principal component analysis. Two-dimensional projection of trajectories showing conformational sampling of the vaccine candidate and vaccine candidateTLR2 and vaccine candidateTLR4 complexes
The Gibbs energy landscape plot during 100 ns of simulation. a The vaccine candidate, b Vaccine candidate-TLR2, c Vaccine candidate-TLR4 complexes
The C-ImmSim server was used to simulate the immune system response to the designed vaccine candidate. Figure7 shows the simulation of the host immune response to the vaccine candidate protein. Antigen and immunoglobulin parameters, cytokine production, TH cell population and B cell population were examined in this evaluation. An increase in IgM levels indicates the initial host response. In addition, a secondary response to the designed protein as antigen is indicated by increased levels of B cell population (Fig.10a), TH cell population (Fig.10b), and IgG1 and IgG2 (Fig.10c). There was also a significant increase in the levels of cytokines and interleukins after immunization, especially interferon- (Fig.10d). Interpretation of the results indicates that the vaccine candidate is capable of stimulating the immune system to produce cytokines and antibodies against T.vaginalis.
In silico immunity simulation against protein antigen designed as a vaccine candidate using C-ImmSim web server. Simulations after three injections at steps 1, 336, and 672 are presented. a B cell population. b TH cell population. c Antigen and immunoglobulin. d Cytokine production
Codon optimization was performed using the JCat tool. After codon optimization, the sequence length of the designed structure was 2352 nucleotides. The codon compatibility index and the GC content of the nucleotide sequence before the optimization were 0.311% and 66.24%, respectively. After codon optimization, the parameters were 1% and 50.73%, respectively (Fig.11a, b). The simulation of the optimized sequence of the vaccine candidate in pET-28a(+) using the SnapGene software showed that the vaccine candidate sequence is clonable in pET-28a(+) (Fig.12a). In the middle of the designed construct, there is a cleavage site for HindIII and BsrGI enzymes, so we set the first and last sequence of the construct with NcoI and XhoI enzymes, respectively. Double digestion with NcoI and XhoI enzymes showed presence of vaccine candidate (2346bp) together with pET-28a(+) vector (5231bp) (Fig.12b).
Codon optimization using the JCat web server. a Before optimization, b after optimization
a Cloning of the designed protein construct into the pET-28a vector (shown in blue). b Informatics evaluation of the cloning of the designed protein by double digest
The human papillomavirus (HPV) vaccine has been shown to significantly reduce the incidence of cervical cancer by nearly 90%1; however, only an estimated 60% of adult women have been vaccinated for HPV.2 Researchers at NYU Langone, including Catherine Herrman, MD, investigated whether offering HPV vaccines at the time of abortion care could increase vaccination rates among women of reproductive age.
The quality improvement initiative was done at a clinic that offers abortion services. The researchers gave staff extra training about HPV and the vaccine. They also created a new system for talking to patients about the vaccine and getting them vaccinated. This system included prompts for doctors to talk to patients about the vaccine, making it easier for patients to get the vaccine during their clinic visit, and reminding patients to come back for the extra shots they need.
Before the new system was in place, about 24% of women who could have gotten the HPV vaccine were counseled, and about 7% started the vaccine series. After the new system was put in place, these numbers went up to 69% and 34%, respectively.3
The researchers also found that most of the women who got the vaccine were Hispanic or Latina and spoke Spanish as a first language.
The study shows that giving HPV vaccines in clinics that offer abortion services is a viable method to get more patients vaccinated for HPV, thus lowering cervical cancer risks for patients as they age.
In an interview with Targeted OncologyTM, Herrman, second-year fellow at NYU Langone, discussed findings and implications from the study she presented at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Womens Health.
Targeted Oncology: What was the rationale behind the study you presented at SGO? Herrman: Despite a lot of data about how effective the HPV vaccine is at preventing cervical cancer, the vaccination rates in the United States are still quite low. Unfortunately, both HPV and cervical cancer are disproportionately affecting women who belong to groups that have been marginalized. To improve that vaccine uptake and help resolve these disparities, we felt like a creative solution was needed, which was why we thought of abortion care. It is common; 1 in 4 women get an abortion during the reproductive years, and it may help capture women earlier in the reproductive years when the vaccine is most likely to be beneficial.
What was the methodology for your analysis?
[We did a] quality improvement study. Before we initiated our workflow, we did a retrospective chart review in the preceding 6 months leading up to when we implemented the study workflow, just to capture our baseline counseling and vaccination rates. Then, we implemented the workflow for 31 weeks that incorporated 4 different tenets. The first was standardizing counseling. To do that, we embedded a standardized note template that everyone could use. We also did some in-person education with providers, and then also provided them with a handout on commonly asked patient questions to help with their counseling. We then also worked with our [post anesthesia care unit] and clinic nursing teams to help streamline same-day vaccinations for patients who were either getting a medical or surgical abortion. We also had a follow-up workflow that consisted of a tracking list that was embedded within the [electronic medical record]. Patients were scheduled by the nurse administering their current vaccine for their follow-up vaccine. We also did reminder texts or phone calls based on patient preference.
Can you discuss your findings?
Before we implemented the workflow, we had 265 patients who were eligible for vaccination in the 6 months leading up to the study. Only 20.3% of those patients were counseled on HPV vaccination. Of the eligible patients, only 6.8% went on to start the series. After we implemented this study, we had 300 patients who were eligible. During the 31 weeks that we had the study running, the counseling rate increased to 68.7%. Of the patients who are counseled, 63% accepted it. Among the patients who accepted it, 78.5% received at least 1 dose. Our overall rate of patients who were eligible who then received at least 1 dose of the vaccine went from 6.8% to 34%.
During the study period, our data on completing the vaccine series [are not] fully mature yet. We are still waiting on several [patients] to determine whether or not they have completed it. But we have had 41.4% of the 99 patients who were due for a subsequent dose come back to get at least 1 additional dose and we've had 13 patients who have completed the series.
Were there any patients subgroups where this initiative appeared particularly effective?
We did not do any sort of subgroup analysis, but I will say that our cohort was quite diverse. We naturally sort of had a breakdown of what some people might consider subgroups in other studies. Our median age was 30. The most common language among the patients who were vaccinated with Spanish; that was 66% of patients. We had self-identified ethnicity data on 50 of the patients. The most common was Ecuadorian, that was at 41%. We also had Mexican at 12%, and Dominican at 8%. We had a very diverse group of patients.
What are the implications of these findings for patients and clinicians?
I think the conclusions we can draw from this is that it is feasible and effective to implement an HPV vaccine workflow into an abortion clinic. I think it speaks to the fact that abortion care is a huge opportunity to address vaccination gaps in reproductive-age patients. We know from the population that we implemented this in that it can be effective among patients who are very under resourced and those patients who are most at risk for cervical cancer disparities. I think it is a call to action for referral centers who are still performing abortions. The states that have implemented abortion bans tend to be the states that also have the lowest rates of HPV vaccination. As patients are coming from those states to get abortions, we now have the opportunity to address 2 disparities at once. I think that's a something that we need to be mindful of as providers.
WHO recommends that HWs be vaccinated against a number of antigens ([i]). Globally, countries have most frequently reported vaccinating HWs against hepatitis B, seasonal influenza and measles ([ii]). In particular, the COVID-19 pandemic has drawn global attention to the importance of vaccinating health and workers (HWs). Countries are expressing interest in building from their experiences deploying COVID-19 vaccination to develop or strengthen national HW vaccination programmes.
WHO headquarters, regional, and country offices have worked closely with ministries of health to document examples from Argentina, Mongolia, Oman, Paraguay and Thailand. These vignettes provide illuminating snapshots of national HW vaccination programmes and have been published here: Influenza health worker vaccination programmes: platforms for pandemic preparedness
This new publication documents countries experiences leveraging HW vaccination for seasonal influenza and other vaccine-preventable diseases to support COVID-19 vaccine introduction. In addition, it provides insight into the structure, motivations, and value of the HW vaccination programmes. A brief overview of key themes identified in the five country vignettes include:
[i]. Table 4: Summary of WHO position papers immunization of health care workers. In: WHO/Publications [website]. Geneva: World Health Organization (https://www.who.int/publications/m/item/table-4-who-recommendations-for-routine-immunization, accessed 30 August 2023).
[ii]. Young S, Goldin S, Dumolard L, Shendale S, McMurren B, Maltezou HC et al. National vaccination policies for health workers a cross-sectional global overview. Vaccine. 2023 Jun 13:S0264-410X(23)00518-2 (https://pubmed.ncbi.nlm.nih.gov/37321897/, accessed 30 August 2023).
Topline
HPV vaccination rates are the lowest among Hispanics, males and Americans with low education levels, according to a new study, and the reasons may include lack of knowledge surrounding HPV including a misconception that it a womens vaccine.
Hpv vaccine in doctors hand
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The human papillomavirus (HPV) is the most common sexually transmitted infection in the U.S., and although it can lead to certain types of cancers later on in life, most infections go away on their own without symptoms.
The HPV vaccine was initially recommended by the Food and Drug Administration for use in children between 11 and 12, and for catch-up vaccinations for those up to 26 years old, but the FDA expanded use in adults between 27 and 45 in 2018.
The researchers reviewed health data between 2018 and 2019 from 9,440 participants aged 27 to 45, and discovered males, Hispanics and lower-income participants were the least likely to be vaccinated against HPV, according to the study published Thursday in Human Vaccines & Immunotherapeutics.
Women were three times more likely to be vaccinated compared to men, and Nosayaba Osazuwa-Peters, lead author and a head and neck cancer epidemiologist at the Duke University School of Medicine, said in a statement men are in particular need of increased knowledge of the vaccine, since anal and oropharyngeal cancer rates, which are known to originate from the HPV virus, are on the rise.
Only about 12% of Hispanic participants were vaccinated against HPV, and the researchers found they were 27% less likely to be vaccinated compared to non-Hispanic whites, while non-Hispanic Blacks were 36% more likely to get vaccinated.
Participants who only had a high school diploma or who had finished some college were also less likely to be vaccinated compared to those with at least one degree, according to the study.
42 million. Thats how many Americans are infected with the types of HPV known to cause disease, according to the Centers for Disease Control and Prevention. Around 13 million American adults and children are infected each year.
The HPV vaccine is a series of two or three shots, and was first approved in 2006 for only women, five years before it was approved for use in men. Because of this, the vaccine has historically been known as a womens only vaccine, though men also benefit from it, according to a study published in Preventive Medicine. HPV can cause several types of cancers like cervical and vaginal, but the most common type of cancer it leads to is oropharyngeal, according to the study, and 75% of patients diagnosed with this type of cancer are men. Although vaccination rates among Hispanic teens is high, coverage among Hispanic adults is low, a 2023 study found. The study chalks this up to potential misconceptions among the community, as Hispanic participants were 8% more likely to believe HPV-related misconceptions than non-Hispanic participants. A separate study found Hispanic men and women had the lowest knowledge of HPV, while non-Hispanic white women and men had the highest. The lack of awareness among those with lower education statuses may be the reason for lower vaccination rates. Only 40% of adults with less than a high school education are aware of HPV, compared to 78% of adults with a college degree or higher, a JAMA Network Open study found.
Religious reason may also be the cause of low HPV vaccination rates, as some religious leaders advise against getting vaccinated since they believe it promotes premarital sex, according to a Current Oncology study. Research also shows the Covid pandemic may have affected HPV vaccination rates. Researchers examined HPV vaccination rates in young adults in 2018, 2019 and 2022, and found that although rates increased between 2018 and 2019, there was no significant change between 2019 and 2022. They concluded the pandemic disrupted young adults from starting the shot series. Overall negative sentiments toward vaccines following the Covid pandemic may also play a role. Some 3% of kids entering kindergarten for the 2022-2023 school year had exemptions for vaccination, which is the highest rate ever reported in U.S. history. Although health agencies have found the coronavirus vaccines to be safe and effective, experts believe the uptick of vaccine exemptions among children is related to skepticism of the updated Covid vaccines approved for use in 2023. Public perception of the importance of childhood vaccines declined in 52 out of 55 countries studied during the Covid pandemic, according to UNICEF.
I'm a Texas native covering the latest trends in tech, science and healthcare through explainer pieces on the breaking news team. Previously, I was a Forbes HBCU Scholar writing under the innovation and health and science teams. In 2022, I graduated from Clark Atlanta University where I was the fashion editor for CAU's official newspaper, the Panther, and the managing editor of Her Campus CAU. During my matriculation, I interned with top companies such as Warner Bros. Discovery and The Walt Disney Company. Got a tip? Don't hesitate to reach out to me via email (ajohnson@forbes.com), or dm me on any social media platform.
