Virus World

A new vaccine for dengue received prequalification from the World Health Organization (WHO) on 10 May 2024. TAK-003 is the second dengue vaccine to be prequalified by WHO. Developed by Takeda, it is a live-attenuated vaccine containing weakened versions of the four serotypes of the virus that cause dengue. 

WHO recommends the use of TAK-003 in children aged 6–16 years in settings with high dengue burden and transmission intensity. The vaccine should be administered in a 2-dose schedule with a 3-month interval between doses.  “The prequalification of TAK-003 is an important step in the expansion of global access to dengue vaccines, as it is now eligible for procurement by UN agencies including UNICEF and PAHO,” said Dr Rogerio Gaspar, WHO Director for Regulation and Prequalification.  “With only two dengue vaccines to date prequalified, we look forward to more vaccine developers coming forward for assessment, so that we can ensure vaccines reach all communities who need it.” The WHO prequalification list also includes CYD-TDV vaccine against dengue developed by Sanofi Pasteur.  Dengue is a vector-borne disease transmitted by the bite of an infected mosquito. Severe dengue is a potentially lethal complication which can develop from dengue infections.  It is estimated that there are over 100-400 million cases of dengue worldwide each year and 3.8 billion people living in dengue endemic countries, most of which are in Asia, Africa, and the Americas. The largest number of dengue cases reported was in 2023 with the WHO Region of the Americas reporting 4.5 million cases and 2300 deaths. Dengue cases are likely to increase and expand geographically due to climate change and urbanization.

Researchers at UC Riverside have developed a new vaccine approach using RNA that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised. Every year, researchers try to predict the four influenza strains that are most likely to be prevalent during the upcoming flu season. And every year, people line up to get their updated vaccine, hoping the researchers formulated the shot correctly. The same is true of COVID vaccines, which have been reformulated to target sub-variants of the most prevalent strains circulating in the U.S. This new strategy would eliminate the need to create all these different shots, because it targets a part of the viral genome that is common to all strains of a virus. The vaccine, how it works, and a demonstration of its efficacy in mice is described in a paper published today in the Proceedings of the National Academy of Sciences.

“What I want to emphasize about this vaccine strategy is that it is broad,” said UCR virologist and paper author Rong Hai. “It is broadly applicable to any number of viruses, broadly effective against any variant of a virus, and safe for a broad spectrum of people. This could be the universal vaccine that we have been looking for. Traditionally, vaccines contain either a dead or modified, live version of a virus. The body’s immune system recognizes a protein in the virus and mounts an immune response. This response produces T-cells that attack the virus and stop it from spreading. It also produces “memory” B-cells that train your immune system to protect you from future attacks. The new vaccine also uses a live, modified version of a virus. However, it does not rely on the vaccinated body having this traditional immune response or immune active proteins — which is the reason it can be used by babies whose immune systems are underdeveloped, or people suffering from a disease that overtaxes their immune system. Instead, this relies on small, silencing RNA molecules.

Mechanism and Efficacy of RNA-Based Vaccine

“A host — a person, a mouse, anyone infected— will produce small interfering RNAs as an immune response to viral infection. These RNAi then knock down the virus,” said Shouwei Ding, distinguished professor of microbiology at UCR, and lead paper author. The reason viruses successfully cause disease is because they produce proteins that block a host’s RNAi response. “If we make a mutant virus that cannot produce the protein to suppress our RNAi, we can weaken the virus. It can replicate to some level, but then loses the battle to the host RNAi response,” Ding said. “A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system.” When the researchers tested this strategy with a mouse virus called Nodamura, they did it with mutant mice lacking T and B cells. With one vaccine injection, they found the mice were protected from a lethal dose of the unmodified virus for at least 90 days. Note that some studies show nine mouse days are roughly equivalent to one human year.

There are few vaccines suitable for use in babies younger than six months old. However, even newborn mice produce small RNAi molecules, which is why the vaccine protected them as well. UC Riverside has now been issued a US patent on this RNAi vaccine technology. In 2013, the same research team published a paper showing that flu infections also induce us to produce RNAi molecules. “That’s why our next step is to use this same concept to generate a flu vaccine, so infants can be protected. If we are successful, they’ll no longer have to depend on their mothers’ antibodies,” Ding said.  Their flu vaccine will also likely be delivered in the form of a spray, as many people have an aversion to needles. “Respiratory infections move through the nose, so a spray might be an easier delivery system,” Hai said. Additionally, the researchers say there is little chance of a virus mutating to avoid this vaccination strategy. “Viruses may mutate in regions not targeted by traditional vaccines. However, we are targeting their whole genome with thousands of small RNAs. They cannot escape this,” Hai said. Ultimately, the researchers believe they can ‘cut and paste’ this strategy to make a one-and-done vaccine for any number of viruses. “There are several well-known human pathogens; dengue, SARS, COVID. They all have similar viral functions,” Ding said. “This should be applicable to these viruses in an easy transfer of knowledge.”

Publised in PNAS (April 17, 2024):

https://doi.org/10.1073/pnas.2321170121

Highlights

Summary

Despite its elimination in the US in 2000, measles cases are being reported across the country. As of February 22, 35 cases have been reported this year in Arizona, California, Florida, Georgia, Indiana, Louisiana, Maryland, Minnesota, Missouri, New Jersey, New York City, Ohio, Pennsylvania, Virginia, and Washington, according to the US Centers for Disease Control and Prevention (CDC). The CDC cautioned in a January alert that between December 1, 2023, and January 23, 2024, the agency was informed of 23 confirmed cases, most among children and adolescents who were eligible for vaccination but had not received the vaccine. Seven of those cases were imported by international travelers—travel-related cases present a danger to people who are unvaccinated and undervaccinated.

Tina Tan, MD, president-elect of the Infectious Diseases Society of America, said it’s important to understand how quickly measles can spread. “We live in a very mobile world where I don’t think people realize that an infectious disease can travel from one side of the world to the other in less than 24 hours,” she said in an interview with JAMA. According to the CDC, clinicians should especially watch for measles symptoms among patients who traveled abroad to countries with ongoing outbreaks. As of early February, Yemen, Azerbaijan, Kazakhstan, India, Ethiopia, and Russia had the world’s highest case numbers.

A single-dose dengue vaccine produced by Butantan Institute in São Paulo state (Brazil) prevents development of the disease in 79.6% of those vaccinated, according to an article published in The New England Journal of Medicine . Called Butantan-DV, the vaccine contains attenuated versions of all four dengue virus serotypes. The results of the ongoing Phase 3 trial show that it is safe and effective for all age groups between 2 and 59, and for people with or without a prior history of infection by dengue virus. "Publication of the article in the world's leading medical journal attests to the rigor and quality of the work done by researchers at 16 Brazilian centers located in all five regions of the country, and coordinated by Butantan Institute," infectious disease specialist Esper Kallás, first author of the article, told Agência FAPESP. "In June, we'll complete the five-year follow-up period. Once the data has been consolidated, we'll know how long the protection induced by the vaccine will last." Also according to Kallás, who heads Butantan Institute, the researchers plan to submit a report to ANVISA, Brazil's health surveillance agency, in the second half of this year in order to apply for registration of the vaccine.

"If all goes well, we'll win definitive approval for the vaccine in 2025. We already have the infrastructure to produce it at Butantan Institute, although it can still be perfected. After all, it's tetravalent, corresponding to four vaccines in one," he said. The article published today describes the results of the first two years of the Phase 3 clinical trial, which began in February 2016 and involves 16,235 participants in 13 states. Preliminary data disclosed by Butantan Institute in December 2022 pointed to overall efficacy of 79.6%. The results for each subgroup evaluated have now been detailed. Vaccine efficacy was 80.1% for participants aged 2-6, 77.8% for those aged 7-17, and 90.0% for 18-59 age group. Stratification by serological status showed protection for 73.6% of participants with no evidence of prior infection by dengue virus and 89.2% of those previously exposed to the virus. Efficacy was 89.5% against dengue serotype 1 (DENV-1) and 69.6% against serotype 2 (DENV-2). It was not possible to assess the vaccine's efficacy against serotypes 3 and 4 because they were not circulating during the follow-up period. Most adverse side effects were classified as mild or moderate. The main reactions were pain and redness at the injection site, headache, and fatigue. Severe adverse events relating to the vaccine were recorded for under 0.1% of all those vaccinated, and all of them recovered. "Findings from Phase 2 [the previous clinical trial] showed that the four attenuated viral serotypes in Butantan-DV multiply in the human organism and induce a balanced response in terms of antibody production. This leads us to conclude that its efficacy against DENV-3 and DENV-4 will also be good," said virologist Maurício Lacerda Nogueira, one of the coordinators of the trials.

Publication cired in N.E.J.M. (Feb. 1, 2024):

https://doi.org/10.1056/NEJMoa2301790 

Using a DNA-based delivery particle, researchers created a vaccine that can induce a strong antibody response against SARS-CoV-2. The vaccine, which has been tested in mice, consists of a DNA scaffold that carries many copies of a viral antigen. This type of vaccine, known as a particulate vaccine, mimics the structure of a virus. Most previous work on particulate vaccines has relied on protein scaffolds, but the proteins used in those vaccines tend to generate an unnecessary immune response that can distract the immune system from the target. In the mouse study, the researchers found that the DNA scaffold does not induce an immune response, allowing the immune system to focus its antibody response on the target antigen.

 “DNA, we found in this work, does not elicit antibodies that may distract away from the protein of interest,” says Mark Bathe, an MIT professor of biological engineering. “What you can imagine is that your B cells and immune system are being fully trained by that target antigen, and that’s what you want — for your immune system to be laser-focused on the antigen of interest.”

PULLMAN, Wash. — A new mobile phone-based facial recognition application for dogs has the potential to significantly improve rabies vaccination efforts in endemic areas like Africa and Asia, according to a study on the research published in the journal Scientific Reports. Led by researchers at Washington State University, a team used the app to test its effectiveness at a rabies vaccination clinic in rural Tanzania where they microchipped, vaccinated and registered dogs. The technology proved remarkably accurate during a subsequent visit to surrounding villages once poor images and improperly recorded information were removed from its database. Using the app, operators identified 76.2% of vaccinated dogs and 98.9% of unvaccinated dogs. “Because domestic dogs are the main reservoir for human rabies, controlling human rabies globally requires the mass vaccination of dogs,” WSU Associate Professor Felix Lankester, the principal investigator of the study, said. “When carrying out mass vaccination, one of the major problems that we face is trying to identify which dogs have and haven’t been vaccinated. For example, microchips are too expensive to use at the scales needed to eliminate rabies, and collars can be removed by owners. We developed this app to see if facial recognition might work, and it’s showing great promise in helping us to achieve that goal.”

Rabies kills an estimated 60,000 people annually. Nearly all cases occur in Africa and Asia, and more than 99% are the result of dog bites. Systematic and consistent vaccination efforts, like those led by WSU’s Rabies Free Africa program, are effective at controlling the disease, but approximately 40% of dogs in an area must be vaccinated at any one time to achieve herd immunity and prevent sustained virus transmission. This makes the ability to accurately and efficiently identify vaccinated dogs vital for successful rabies elimination programs. The facial recognition algorithm used within the application, developed in collaboration with PiP My Pet, a company located in Vancouver, Canada, and researchers in WSU’s Paul G. Allen School for Global Health, identifies a dog by examining key components of its face and comparing it to images of the faces of other dogs in its archive of previously stored images. Images with the highest number of similar components are returned as possible matches, and the user must decide if there is a match.

The app depends on image quality and information about each dog, including its age, color and sex, being properly recorded. Before poor quality images and incorrect information were removed from the database, users were only able to match 65% of the vaccinated dogs. Lankester, who also serves as a director of Rabies Free Africa, said the app’s effectiveness could be improved with better technology – like newer smartphones with high-quality cameras – and additional operator training. In addition to its potential as a tool in identifying vaccinated dogs, the technology holds promise for use in other species, disease control efforts and research purposes where animals might need to be identified. Currently, users must be online to operate the facial matching component, however, Lankester said the team is also working to compress the size of the “engine” that drives the app’s matching facility to allow it to be downloaded and used offline, which would reduce the app’s reliance on internet access, which is not always available in more remote areas. “We’re not quite there yet, but I think with investment, the technology  can get there. I’m excited by its potential,” Lankester said, “but we have to find some funding to invest in pushing it forward. I welcome people to get in touch if they have funding ideas or would like to collaborate on this.”

Research published in Scientific Reports (Dec. 12, 2023):

https://doi.org/10.1038/s41598-023-49522-2 

We present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 vaccination campaign using XBB.1.5 vaccine against COVID-19 hospitalization and ICU admission in previously vaccinated adults ≥60 years old in the Netherlands. We compared vaccination status of 2050 hospitalizations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalization was 70.7% (95% CI: 66.6; 74.3), VE against ICU admission was 73.3% (95% CI: 42.2; 87.6).

Preprint in medRxiv (Dec. 13, 2023):

https://doi.org/10.1101/2023.12.12.23299855 

Study published in Nature Immunology reveals that repeated mRNA COVID-19 vaccinations enhance immune response, especially in previously infected individuals, leading to a diversified and increased number of immune cell clones and a stronger ability to combat various virus strains. In a recent study published in the journal Nature Immunology, researchers investigated how repeated mRNA vaccinations improve COVID-19 immunity in SARS-CoV-2-naïve and priorly infected individuals. Focusing on the latter cohort, the study evaluated the diversity and concertation in tandem with multiple sequencing analyses of immune cells isolated from the patient’s peripheral blood mononuclear cells. Study findings reveal that sequential vaccination promotes heterogeneous immune cell clonal expansions, with the third mRNA vaccination resulting in almost two times the number of clones as the first vaccination dose. Parallelly, populations of CD8+ T cells substantially increase, thereby better preparing an individual’s immune system to cope with multiple COVID-19 strains. Surprisingly, the presence and severity of COVID-19 infection were directly associated with post-vaccination immunity.

Does infection prevent infection?

First, a disclaimer – under no circumstances are the authors of the publication or the author of this article recommending that you allow yourself to become infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a means of improving your future immunity against the Coronavirus disease 2019 (COVID-19) pandemic. However, a number of previous studies have established the improved anti-COVID-19 capabilities of ‘hybrid immunity.’ Hybrid immunity arises from the combined effects of both a previous COVID-19 infection and vaccination, which have been consistently found to confer better protection than either alone. Two main mechanisms for this improved observed immunity have been proposed – an increase in the abundance and diversity of virus-specific memory T (Tm) cells and an increased diversity of spike (S) proteins in the Tm cell pool. Hitherto, however, these hypotheses have never been scientifically tested. Understanding the mechanisms underpinning observed immune responses to COVID-19 in hybrid individuals may allow for improved and personalized vaccination regimes, thereby improving global resistance against the pandemic, which has hitherto infected more than 770 million individuals and cost humanity almost 7 million lives.

About the study

In the present study, researchers used peripheral blood mononuclear cells (PBMCs) to identify and quantify the variations in T and B cell populations across individuals exposed to multiple vaccination doses in tandem with COVID-19 infections of varying severity. They then focused their efforts on evaluating the kinetics and diversity of T spike (Ts) cells, thereby verifying both proposed hypothesized mechanisms underpinning previously observed immunity improvements. The study cohort comprised 54 (28 female) self-reported COVID-19 survivors recruited from Seattle, USA, between April and August 2020. All participants had their demographic and medical data recorded and were subjected to convalescent plasma donation for PBMC isolation. The cohort consisted of 35 individuals with mild to moderate COVID-19, 19 with severe illness (hospital and oxygen support required), and eight with critical COVID-19 (intensive care unit [ICU] admission required). Participants ranged from 31 to 74 years of age, with 60.3 presenting the median value. Participants presented a diverse array of comorbidities, including cancer (n = 8), renal disease (n = 4), heart ailments (n = 9), hypertension (n = 9), and diabetes (n = 9).

From preserved PCMBs, selective staining was used to identify and isolate live CD3+ single cells, single positive CD4−CD8+, and CD4+CD8−, excluding all double positive and negative CD cells from further experiments. Gating and Boolean analyses with PBMC stimulation were used to identify and study AIM assay combinations of antigen-specific (in this case, SARS-CoV-2 Wu-1 strain) T-cell frequency. Intracellular cytokine staining (ICS) was used to identify and quantify the production of cytokines following SARS-CoV-2 stimulation. Genomic DNA isolated from PBMCs was used for T-cell Receptor Sequencing (TCR-Seq), a method used to identify and track specific T cells and their clones. TCR-Seq was carried out independently for bulk repertoire analyses (bulk TCR-Seq) and antibody feature barcode library generation (single-cell TCR-Seq). The library generated above was used for CD4+ and CD8+ assignments using unique molecular identifier (UMI) counts. SARS-CoV-2 Wu-1 strain-transfected Cos-7 cells were used to evaluate the specificity of assigned CD8+ T cells. Finally, next-generation Human Leukocyte Antigen (HLA) Typing was carried out to identify class 1 and class 2 allotypes.

Study findings

Results from the above tests revealed divergent vaccine response kinetics, both between CD4+ and CD8+ TS cells and between individuals with differing COVID-19 disease severity. “In persons with previous SARS-CoV-2 infection, mRNA vaccines induced profound, albeit variable, expansion of preexisting circulating TM cell clones.” These results were amplified based on the number of mRNA vaccines received following COVID-19 disease, with the first two vaccine doses observed to augment S-reactive clonotypic diversity in the blood, resulting in substantial expansion in CD8+ TS clonotypes. A similar expansion in CD8+ TS clonotypes has been reported in COVID-19-naïve individuals following their first vaccination dose, albeit to a much lower extent. This study further revealed that while not as substantial as CD8+ TS clonotype expansion, CD4+ clonotypes also expanded following the second vaccination dose.

Published in Nat. Immunology (Dec. 6, 2023):

https://doi.org/10.1038/s41590-023-01692-x

Nov 30 (Reuters) - Pfizer (PFE.N) has been sued by Texas Attorney General Ken Paxton, who on Thursday accused the drugmaker of misrepresenting the efficacy of its widely-used COVID-19 vaccine. In a complaint filed in a Lubbock County state court, Paxton said it was misleading for Pfizer to claim its vaccine was 95% effective because it offered a "relative risk reduction" for people to who took it. Paxton said the claim was based on only two months of clinical trial data, and vaccine recipients' "absolute risk reduction" showed that the vaccine was just 0.85% effective. He also said the pandemic got worse even after people started taking the vaccine, developed by Pfizer and its German partner BioNTech (22UAy.DE). "Pfizer intentionally misrepresented the efficacy of its COVID-19 vaccine and censored persons who threatened to disseminate the truth in order to facilitate fast adoption of the product and expand its commercial opportunity," the complaint said. The lawsuit seeks to stop New York-based Pfizer from making alleged false claims and silencing "truthful speech" about its vaccine, and more than $10 million in fines for violating a Texas law protecting consumers from deceptive marketing. Pfizer said more than 1.5 billion of people have received its vaccine. The drugmaker has reported more than $74 billion of revenue in 2021 and 2022 related to COVID-19 immunizations.

In a statement, Pfizer said its representations about its vaccine have been "accurate and science-based," and that it believed Paxton's lawsuit had no merit. Pfizer also said its vaccine has "demonstrated a favorable safety profile in all age groups, and helped protect against severe COVID-19 outcomes, including hospitalization and death." Infectious disease experts have said relative risk reduction is a more meaningful way to judge a vaccine's efficacy than absolute risk reduction. Relative risk shows how well a vaccine protects recipients relative to a study's control group. Paxton, a Republican, has criticized Biden administration efforts to fight the pandemic. Earlier this year, he began probing whether Pfizer, Moderna (MRNA.O) and Johnson & Johnson (JNJ.N) misrepresented their vaccines' efficacy, to examine the "scientific and ethical basis" for public health decisions addressing COVID-19. "Pfizer did not tell the truth about their COVID-19 vaccines," Paxton said in a statement. "We are pursuing justice for the people of Texas, many of whom were coerced by tyrannical vaccine mandates to take a defective product sold by lies." The lawsuit is Paxton's second against Pfizer in November. In a case unsealed on Nov. 21, Paxton accused Pfizer and a supplier of manipulating quality control tests, resulting in the distribution of ineffective drugs to treat attention deficit hyperactivity disorder in children. The status of the probe into Moderna and Johnson & Johnson was not immediately clear. Paxton's office did not immediately respond to requests for comment. Reporting by Jonathan Stempel in New York; Additional reporting by Caroline Humer; Editing by Chizu Nomiyama and Daniel Wallis

For cardiologist Eric Topol, this week’s vaccine news presented a personal dilemma. Topol, who directs the Scripps Research Translational Institute and is a popular commenter on COVID-19 research, had hoped to get an updated COVID-19 vaccine from Novavax, rather than a messenger RNA (mRNA) shot from Pfizer or Moderna. Novavax relies on an older, protein-based approach that has shown long-lasting effects against other pathogens, and Topol wondered whether it might produce more durable protection. On Tuesday, it seemed he might get his chance: a drugstore he visited for an mRNA vaccine ran out of doses, and hours later the U.S. Food and Drug Administration authorized a Novavax shot well-matched to current COVID-19 variants. The green light marks the first time Novavax will be widely available to teens and adults. “It’s hard to know how it compares” to mRNA vaccines, Topol admits; there are no head-to-head studies to rely on. In clinical trials, Novavax appeared less likely than mRNA shots to cause side effects like headache and fatigue. But how does it stack up against mRNA vaccines when it comes to protection against SARS-CoV-2? The question has been vexingly difficult to answer.

Some hints are emerging, including the first large study of Novavax in the real world, published this week by a team in Italy. The results are far from definitive, but they suggest “there aren’t massive differences” between the vaccines, says Alberto Mateo Urdiales, an epidemiology and infectious disease researcher at the Italian National Institute of Health, who led the study. Whereas mRNA vaccines carry instructions for making a SARS-CoV-2 protein, Novavax directly delivers a fragment of that viral spike protein with an adjuvant for boosting immune response. Such protein subunit vaccines have yielded durable protection against various pathogens including hepatitis B and shingles, along with some respiratory ailments such as pneumonia. A version of the Novavax vaccine targeting the original SARS-CoV-2 variant was approved as a primary vaccination series and first booster in the United States in 2022; it also became available in Europe that year. Its tried-and-true technology appealed to some people wary of the new mRNA approach. And unlike the more fragile mRNA shots, it lasts for months in the refrigerator. But uptake has been low and the company is banking on more shots in arms this fall.

The Italian team tried to pin down how well the shot actually works, analyzing data on more than 20,000 Italians who had received two doses as their primary vaccine series in 2022. After 4 months, the vaccine was 55% effective at staving off symptoms from a SARS-CoV-2 infection and 28% effective at preventing infection altogether, the researchers reported in JAMA Network Open. That’s roughly comparable to how the mRNA vaccines have performed, Mateo Urdiales says. He cautions that the emergence of SARS-CoV-2 variants, repeated boosting, and swelling numbers of infections make it hard to compare numbers across the studies of effectiveness conducted to date. Smaller studies, meanwhile, have tried to address another reason a Novavax booster appeals to people like Topol: the possibility that “mixing and matching” various COVID-19 vaccines might provide better protection than any single vaccine brand. “There was theoretical hope that since these vaccines work in slightly different ways, they would have different strengths in terms of which part of the immune system they activate best,” says Angela Branche, an infectious disease specialist at the University of Rochester. She co-chairs a mix-and-match study called COVAIL that includes another protein subunit vaccine from the company Sanofi, which is not available in the U.S....

UChicago Pritzker Molecular Engineering research could yield treatments with fewer side effects. A new type of vaccine developed by researchers at the University of Chicago’s Pritzker School of Molecular Engineering has shown that it can reverse autoimmune diseases like multiple sclerosis and type 1 diabetes in lab tests — all without shutting down the rest of the immune system. Trials are only just beginning in humans, but researchers say the method holds promise. “In the past, we showed that we could use this approach to prevent autoimmunity,” said Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering and lead author of the new paper. “But what is so exciting about this work is that we have shown that we can treat diseases like multiple sclerosis after there is already ongoing inflammation, which is more useful in a real-world context.” A typical vaccine teaches the human immune system to recognize a virus or bacteria as an enemy that should be attacked. The new “inverse vaccine” does just the opposite: it removes the immune system’s memory of one molecule. While such immune memory erasure would be unwanted for infectious diseases, it can stop autoimmune reactions like those seen in multiple sclerosis, type I diabetes, or rheumatoid arthritis, in which the immune system attacks a person’s healthy tissues.

Unwinding an immune response

The job of the immune system’s T cells is to recognize unwanted cells and molecules — from viruses and bacteria to cancers — as foreign to the body and get rid of them. Once T cells launch an initial attack against an antigen, they retain a memory of the invader to eliminate it more quickly in the future. T cells can make mistakes, however, and recognize healthy cells as foreign. In people with multiple sclerosis, for instance, T cells mount an attack against myelin, the protective coating around nerves. Today, autoimmune diseases are generally treated with drugs that broadly shut down the immune system. “These treatments can be very effective, but you’re also blocking the immune responses necessary to fight off infections and so there are a lot of side effects,” said Hubbell. Hubbell and his colleagues wanted to explore an alternative approach. They knew that the body has a mechanism for ensuring that immune reactions don’t occur in response to every damaged cell in the body — a phenomenon known as peripheral immune tolerance, which is carried out in the liver. They discovered in recent years that tagging molecules with a sugar known as N-acetylgalactosamine (pGal) could mimic this process, sending the molecules to the liver where tolerance to them develops.

“The idea is that we can attach any molecule we want to pGal and it will teach the immune system to tolerate it,” explained Hubbell. “Rather than rev up immunity as with a vaccine, we can tamp it down in a very specific way with an inverse vaccine.” In the new study, the researchers focused on a multiple-sclerosis-like disease in which the immune system attacks myelin, leading to weakness and numbness, loss of vision and, eventually mobility problems and paralysis. The team linked myelin proteins to pGal and tested the effect of the new inverse vaccine in animals. The immune system, they found, stopped attacking myelin, allowing nerves to function correctly again and reversing symptoms of disease. In a series of other experiments, the scientists showed that the same approach worked to minimize other ongoing immune reactions.

Toward clinical trials

Initial phase I safety trials of a glycosylation-modified antigen therapy based on this preclinical work have already been carried out in people with celiac disease, and phase I safety trials are under way in multiple sclerosis. Those trials are conducted by the pharmaceutical company Anokion SA, which helped fund the new work and which Hubbell cofounded and is a consultant, board member, and equity holder. The Alper Family Foundation also helped fund the research. “There are no clinically approved inverse vaccines yet, but we’re incredibly excited about moving this technology forward,” said Hubbell.

Research cited published (Sept. 7, 2023) in Nat. Biomedical Engineering:

 https://doi.org/10.1038/s41551-023-01086-2 

A massive upsurge in dengue cases marked by multiple outbreaks is occurring worldwide and raising new questions about who is at elevated risk of severe forms of the mosquito-transmitted disease. Incidence of the infection has increased by orders of magnitude throughout the so-called dengue belt, which encompasses Central and South America, Sub-Saharan Africa, Southeast Asia and swaths of the South Pacific, home to densely populated islands. Dengue, without question, is the most widespread and rapidly increasing vector-borne disease in the world, according to the World Health Organization. In the Americas alone, more than 5.2 million cases have been documented and more than 1,000 deaths were reported within the first three months of 2024, the Pan American Health Organization reported in April, noting a marked surge over the same period in 2023. The story is similar in other dengue-affected areas of the world where lapses in vector control have conspired with global climate change to create an explosion of bloodthirsty mosquitoes, swarms of them moving into regions once considered dengue-free. Only female mosquitoes feed on blood, they're in constant need of the nutrients in it to nurture their eggs. Now, more than two decades of dengue surveillance in Thailand is answering a slew of questions at a time when the world needs guidance most. Findings from the research have revealed how various subgroups—what virologists call subtypes—of the dengue virus influence future risk of severe infection. It has been known for years that those who become infected in subsequent outbreaks, after a usually mild bout with a first-time infection, are at significant risk of severe disease in later dengue exposures. New research finally has analyzed more than 15,000 cases to discern why that is so.

Writing in Science Translational Medicine, a global team of scientists has explained how the four dengue viral subtypes—DENV-1, 2, 3, and 4—influence the risk of repeated severe infections. The findings provide a new framework for disease monitoring and lay the foundation for vaccination strategies as the new dengue immunizations emerge. The team also underscored how dengue, a pernicious tropical malady, can be understood within the context of other common viral diseases that circle the globe. "The ability of viruses, such as SARS-CoV- 2 and influenza, to continuously change their genetic structure in response to the selective pressure of population immunity complicates control efforts," said Dr. Lin Wang, lead author of the dengue study. "In the case of dengue virus, an arbovirus that infects more than 100 million people each year, the situation is even more complex," Wang continued. "Individuals with high dengue virus antibody titers are protected from infection and developing severe disease. "However, individuals with sub-neutralizing antibody titers have been shown to have the highest risk of severe disease, through multiple hypothesized mechanisms including antibody-dependent enhancement," emphasized Wang, a researcher in the genetics department at the University of Cambridge in England. A dengue infection can be tricky. Some patients who have weathered an infection but get infected in a subsequent outbreak can have more severe symptoms the second time around. Yet, most research on repeat dengue infections has regarded each of the serotypes as no different from the other, Wang and colleagues contend, noting that an assessment of each serotype's genetic differences was needed to provide a clearer picture of potential risks.

To develop that clearer picture, researchers studied each serotype in more than 15,000 patients' infections as a way to peel away much of the mystery surrounding why first-time dengue illnesses are traditionally milder than subsequent ones. Working with Wang were collaborators from two centers in Bangkok, Thailand; multiple research institutes in the United States and one in France. To determine how each of the viral serotypes affects the risk of severe disease, Wang and colleagues analyzed viral genetic data. The team also studied cases of patients hospitalized for dengue to determine which viral subtype caused their infections. Researchers gathered data from 21 years of dengue surveillance, ranging from 1994 to 2014, in a children's hospital in Bangkok, encompassing 15,281 individual cases. This allowed them to find repeat cases and each viral subtype in all infections. Based on the pediatric patients' hospital records, researchers discovered a link between hospitalization and the order in which patients became infected with different dengue-virus serotypes. They were also able to determine which combinations of viral subtypes pointed to mild or severe forms of dengue. For instance, people who became infected with serotypes that were very similar, such as DENV-3 and DENV-4, or very different serotypes as in the case of DENV-1 and DENV-4, tended to have a lower risk of severe disease during the second infection.  That said, patients who were infected with serotypes that were only moderately different had a higher risk of severe symptoms in subsequent infections. The highest risk group in this category involved patients who had an initial infection with DENV-2 followed by a subsequent infection triggered by DENV-1.

The new research adds clarity to a disease risk that may seem paradoxical to the lay public. For example, most people infected with dengue virus for the first time develop extremely mild signs of the disease or none at all. But for those who do get sick, soaring fever, headache, body aches, nausea and rash are the primary symptoms, and they intensify in severe manifestations of the infection. For more than a century a severe bout with dengue has been known as breakbone fever because of the intensity of the pain and accompanying muscle spasms. The virus is carried in the tropics and subtropics by Aedes aegypti and Aedes albopictus mosquitoes, which are endemic in the dengue belt. But while the belt, which runs through latitudes 35-degrees North and 35-degrees South, has traditionally been home to dengue-carrying mosquitoes, the arthropods have been extending their range northward as global climate change intensifies, scientists say. Wang, meanwhile, reports that the collaborative research has set the stage to better understand immune system function in subsequent, severe dengue infections. "These findings suggest that immune imprinting helps determine dengue disease risk and provides a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines," Wang concluded. "This will become increasingly important as dengue vaccines begin to get used."

Research published in Science Translational Medicine (April 24, 2024):

https://doi.org/10.1126/scitranslmed.adk3259 

The U.S. must act decisively, acknowledging the potential gravity of H5N1 mammalian transmission. Humans have no natural immunity to the bird flu virus. 

The recent detection of H5N1 bird flu in U.S. cattle, coupled with reports of a dairy worker contracting the virus, demands a departure from the usual reassurances offered by federal health officials. While they emphasize there’s no cause for alarm and assert diligent monitoring, it’s imperative we break from this familiar script. H5N1, a strain of the flu virus known to infect bird species globally and several mammalian species in the U.S. since 2022, has now appeared to have breached a new barrier of inter-mammalian transmission, as exemplified by the expanding outbreak in dairy cows in several jurisdictions linked to an initial outbreak in Texas. Over time, continued transmission among cattle is likely to yield mutations that will further increase the efficiency of mammal-to-mammal transmission. As the Centers for Disease Control continues to investigate, this evolutionary leap, if confirmed, underscores the adaptability of the H5N1 virus and raises concerns about the next step required for a pandemic: its potential to further evolve for efficient human transmission. Because humans have no natural immunity to H5N1, the virus can be particularly lethal to them. Despite assertions of an overall low risk of H5N1 infection to the general population, the reality is that the understanding of this risk is limited, and it’s evolving alongside the virus. The situation could change very quickly, so it is important to be prepared.

Comparisons to seasonal flu management underestimate the unique challenges posed by H5N1. Unlike its seasonal counterparts, vaccines produced and stockpiled to tackle bird flu were not designed to match this particular strain and are available in such limited quantities that they could not make a dent in averting or mitigating a pandemic, even if deployed in the early stages to dairy workers. The FDA-approved H5N1 vaccines — licensed in 2013, 2017, and 2020 — do not elicit a protective immune response after just one dose. Even after two doses, it is unknown whether the elicited immune response is sufficient to protect against infection or severe disease, as these vaccines were licensed based on their ability to generate an immune response thought to be helpful in preventing the flu. Early studies done by mRNA vaccine companies on seasonal flu are promising, which could be good news here since mRNA vaccines can be made more quickly than vaccines using eggs or cells. Congressional funding is needed to catalyze rapid vaccine development and production. While FDA-approved antiviral drugs like Tamiflu and Xofluza could be an important line of defense against H5N1, logistical barriers impede their timely administration, as they work best when given as early as possible within 48 hours of the onset of symptoms. Most Americans would find it challenging to get a prescription filled for these medicines within the optimal time frame. Streamlining access to stockpiled antiviral drugs through improved test-to-treat measures like behind-the-counter distribution or dedicated telemedicine consultations could vastly improve their effectiveness as a frontline defense. Making plans to do that need to start now.

For vulnerable people — older adults and anyone who is immunocompromised — clinicians have become accustomed to relying on monoclonal antibodies. Sadly, their performance for flu has been disappointing in many clinical trials and can’t be counted on. The need for robust diagnostic capabilities cannot be overstated. H5N1 will not be detected by the typical rapid flu antigen tests that are administered in emergency rooms and many doctors’ offices. New tests will have to be made from scratch. The dismantling of diagnostic infrastructure post-Covid-19 and supply chain disruptions, however, pose significant challenges to the availability of such tests. Rapid investment in diagnostic testing, coupled with efforts to secure essential materials, is imperative to ensure timely detection and antiviral treatment. President Biden’s emphasis on infrastructure presents a unique opportunity to fortify America’s defenses against infectious diseases. A national initiative to enhance indoor air quality in schools and communal spaces could mitigate transmission risks should this virus learn how to efficiently be transmitted between humans, and would pay dividends every respiratory virus season and for years to come. In the face of uncertainty, complacency is not an option. The U.S. must act decisively, acknowledging the potential gravity of the H5N1 situation while leveraging every available resource to safeguard public health. The stakes are too high to repeat past mistakes.

Luciana Borio is an infectious disease physician, a senior fellow for global health at the Council on Foreign Relations, a venture partner at ARCH Venture Partners, and former director for medical and biodefense preparedness policy at the National Security Council. Phil Krause is a virologist, infectious disease physician, and former deputy director of the Office of Vaccines Research and Review at the FDA. The authors have no links to any companies producing or evaluating any of the vaccines or therapies mentioned in this article, and declare no conflicts of interest.

Explore the latest developments in Multiple Sclerosis research, focusing on the potential of a vaccine targeting the Epstein-Barr Virus. Learn about the impact of EBV on MS and the groundbreaking efforts towards vaccine development. Recent scientific advancements have brought hope in the fight against Multiple Sclerosis (MS), a debilitating neurological condition affecting millions worldwide. Key to this optimism is the potential development of a vaccine targeting the Epstein-Barr Virus (EBV), a common factor in nearly all MS patients.

Understanding Multiple Sclerosis and EBV

Multiple Sclerosis is an autoimmune disease that leads to the destruction of myelin, the protective sheath surrounding nerve fibers. This results in a wide range of symptoms, including severe physical disability. The exact cause of MS remains unknown, but the link between MS and the Epstein-Barr Virus, known for causing mononucleosis, has been extensively documented. Research suggests that MS may develop when the immune system attacks myelin in the nervous system, confused by molecular similarities between myelin proteins and those produced by EBV.

Groundbreaking Research and Vaccine Development

A pivotal study tracking American military personnel revealed a significantly higher rate of EBV antibodies in those diagnosed with MS, reinforcing the virus's role in the disease's development. This discovery has led to the exploration of antiviral therapies aimed at reducing EBV in the immune system. Notably, Moderna and the National Institute of Allergy and Infectious Diseases are at the forefront, developing vaccines focused on the gp350 protein of EBV. Though the journey to a comprehensive solution is ongoing, these efforts represent a significant leap towards potentially eradicating MS.

The Road Ahead

As the scientific community rallies behind these promising developments, the implications for MS treatment and prevention are profound. However, the effectiveness of these vaccines in preventing MS remains to be fully assessed, with years of research ahead. The potential for a world where MS can be prevented or substantially mitigated is on the horizon, thanks to these innovative strategies targeting the root causes of the disease. The battle against Multiple Sclerosis is entering a hopeful phase, with groundbreaking approaches offering a glimpse into a future where this devastating disease could be significantly controlled or even eliminated. While challenges remain, the dedication and innovation of researchers worldwide signal a potentially transformative era in MS treatment and prevention.

Effectiveness of the 2023-2024 vaccine lands at 54% for symptomatic cases. The updated 2023-2024 COVID-19 vaccine was approximately 54% effective against symptomatic SARS-CoV-2 infection in adults, and was also effective against the JN.1 variant, which became predominant in January, CDC researchers said. Overall, vaccine effectiveness against symptomatic COVID was 57% for people ages 18 to 49 years and 46% for people ages 50 and older, reported Ruth Link-Gelles, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and colleagues in the Morbidity and Mortality Weekly Reportopens in a new tab or window.

The updated vaccine is a monovalent XBB.1.5-derived vaccine, and there have been few estimates regarding its effectiveness, the authors noted. This study is the first to look at the vaccine's effectiveness against symptomatic COVID caused by the JN.1 variantopens in a new tab or window, a derivative of BA.2.86. The data came from the CDC's Increasing Community Access to Testing program that provided no-cost SARS-CoV-2 nucleic acid amplification tests (NAAT) to uninsured people at participating CVS and Walgreens pharmacies from Sept. 21, 2023 to Jan. 14, 2024. Vaccine effectiveness was 58% among those who received testing 7 to 59 days after receiving the updated vaccine, and 49% among those who received testing 60 to 119 days after receipt.

Coronavirus Disease 2019 (COVID-19) vaccines protect the public and limit viral spread. However, inactivated viral vaccines use the whole virus particle, which contains many non-capsid proteins that may cause adverse immune responses. A report has found that the ADP-ribose-binding domains of SARS-CoV-2 non-structural protein 3 (NSP3) and human poly(ADP-ribose) polymerase family member 14 (PARP14) share a significant degree of homology. Here, we further show that antibodies against 2019 novel SARS-like coronavirus (SARS-CoV-2) NSP3 can bind human PARP14 protein. However, when G159R + G162R mutations were introduced into NSP3, the antibody titer against human PARP14 decreased 14-fold.

Antibodies against SARS-CoV-2 NSP3 can cross-react with human skeletal muscle cells and astrocytes, but not human embryonic kidney 293T cells. However, when G159R + G162R mutations were introduced into NSP3, the cross-reaction was largely inhibited. The results imply that COVID-19 patients with high antibody titers against NSP3 may have high risks of muscular and/or neurological complications. And the possible strategies to improve the safety of inactivated viral vaccines are also discussed.

Published in Vaccine (Jan. 27, 2024): https://doi.org/10.1016/j.vaccine.2024.01.074

Researchers from Karolinska Institutet in Sweden have discovered that the gut microbiome can influence how well people respond to mRNA COVID vaccines. The study, published in the journal npj Biofilms and Microbiomes, suggests that certain bacteria in the gut can enhance the immune response to the vaccine, whereas other bacteria may weaken it. The gut microbiome is the collection of microorganisms that live in our digestive tract. It plays an important role in many aspects of our health, such as digestion, metabolism, and immunity. The researchers wanted to find out if the gut microbiome also affects the response to mRNA COVID vaccines. To do this, the researchers collected stool samples from 68 people living with HIV and 75 healthy individuals before their first mRNA COVID vaccine dose. The researchers analysed the microbiome composition using a technique called 16S rRNA sequencing, which identifies the types and relative abundance of bacteria in the samples. They also measured the levels of antibodies and immune cells that were produced after the vaccination.

The results showed that the initial makeup of the gut microbiome could predict the immune response to the vaccine in both groups. They found that a less diverse gut microbiome was associated with a stronger vaccine response, marked by higher levels of spike protein antibodies and spike specific CD4 T-cells. These are key components of the immune system that help to neutralize the virus and prevent severe infection. The researchers also identified specific bacteria that were linked with better or worse vaccine responses. For example, they found that Lactobacillus, Bacteroides, and Lachnospira were associated with higher antibody and immune cell levels, while Cloacibacillus was associated with lower antibody levels. They also found that Bifidobacterium and Faecalibacterium were microbial markers of individuals with higher antibody levels.

According to the researchers, the study highlights the significant role of the gut microbiome in the effectiveness of mRNA COVID vaccines. The findings could lead to developing microbiota-focused treatments to enhance vaccine responses, especially in groups that may have weaker responses, such as the elderly or immunocompromised individuals. The potential strategies could include changing the diet or taking probiotics to improve the gut microbiome and immunity, the researchers suggest. The study was conducted in collaboration with the Karolinska University Hospital, and SciLifeLab National Genomics Infrastructure in Stockholm, Sweden. The research was funded by Region Stockholm, the Swedish Research Council, and Physicians Against AIDS.

Cited study published in NPJ Biofilms and Microbiomes (Dec. 20, 2023):

https://doi.org/10.1038/s41522-023-00461-w 

A new paper in Biology Methods & Protocols indicates that researchers in Germany have developed a new system to display epitopes in mammal cells for immunization studies. They believe that this method can help scientists greatly in immunization efforts. Promoting blood cells to produce antibodies against a specific viral protein is an important step in developing vaccines for human use. This can be challenging for researchers because whether the subjects develop antibodies depends on how scientists design and administer antigens, which are parts of the virus they're administering to test the effectiveness of the vaccine. One very important aspect of virus research is how to express and purify the antigen for vaccination. Animals immunized with prepared antigens produce specific antibodies against the antigen. But scientists have to isolate the antigen to ensure that they develop the vaccine to target the specific disease they wish to combat. Once researchers purify the antigen, they can develop vaccines that lead subjects to produce the desired antibodies. But this isolation is especially time-consuming when attempting to develop lab-produced antigens as a virus often mutates rapidly. It can take several weeks for scientists to develop the right antigens. Here scientists developed a new method to induce target-specific immune responses. By fusing antigen proteins into a tetraspanin-derived anchor membrane-bound protein, the researchers created fusion proteins that are displayed predominantly on the surface of human cells.

The exposition of proteins on the surface by a carrier protein induces the production of antibodies directed against the appropriate, relevant, antigens. Of additional advantage is that these antigens have the same conformation and modifications as the corresponding proteins in the virus because they are made by cells similar to that in the human body, which the virus infects naturally. This new display technology could be a potentially much more reliable immunization technique. In the study here the researchers were able to induce antibodies against different proteins with a focus on the receptor-binding domain of SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19). The developed anchor protein allows scientists to target a specific disease for immunization purposes without the need to purify the antigen. The researchers are convinced that this technique can speed up the immunization process enormously. "This work is based on the receptor binding domain of SARS-CoV-2 and is only the beginning of a very interesting immunization technique," said Daniel Ivanusic, one of the paper's authors. "The most challenging, significant, and exciting application for us employing the tANCHOR technology is to induce neutralizing antibodies against HIV-1. I think this will be great."

research published (Dec. 12, 2023) in Biology Methods and Protocols

 https://doi.org/10.1093/biomethods/bpad030 

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3–5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination.

The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization. A study demonstrates that nucleotide modifications in mRNA-based therapeutics can lead to +1 ribosomal frameshifting during translation, yielding products that can trigger immune responses.

Published in Nature (Dec. 6, 2023):

https://doi.org/10.1038/s41586-023-06800-3 

The mosquito-borne disease, which can be fatal to newborns, has killed at least 350 people this year. The FDA's approval is expected to speed up the vaccine's global rollout. This year, about 440,000 chikungunya cases, including 350 deaths, have been reported as of September. There is currently no specific drug to treat chikungunya. South America and South Asia have seen the most number of cases this year. The vaccine named Ixchiq has been approved for those aged 18 and above and are at high risk of contracting the disease, the FDA said on Friday. It was developed by Europe's Valneva and will be administered in a single shot. "Infection with chikungunya virus can lead to severe disease and prolonged health problems, particularly for older adults and individuals with underlying medical conditions," senior FDA official Peter Marks said.

Katalin Karikó and Drew Weissman laid the groundwork for immunizations that were rolled out during the pandemic at record-breaking speed. This year’s Nobel Prize in Physiology or Medicine has been awarded to biochemist Katalin Karikó and immunologist Drew Weissman for discoveries that enabled the development of mRNA vaccines against COVID-19. The vaccines have been administered more than 13 billion times, saved millions of lives and prevented millions of cases of severe COVID-19, said the Nobel committee. Karikó, who is at Szeged University in Hungary, and Weissman, at the University of Pennsylvania in Philadelphia (UPenn), paved the way for the vaccines’ development by finding a way to deliver genetic material called messenger RNA into cells without triggering an unwanted immune response. They will each receive an equal share of the prize, which totals 11 million Swedish krona (US$1 million). Karikó is the 13th female scientist to win a Nobel Prize in medicine or physiology. She was born in Hungary, and moved to the United States in the 1980s. “Hopefully, this prize will inspire women and immigrants and all of the young ones to persevere and be resilient. That’s what I hope,” she tells Nature.

A new chapter

The COVID-19 vaccines developed by Moderna and the Pfizer–BioNTech collaboration deliver mRNA that instructs cells to create copies of a protein that is found on SARS-CoV-2 virus particles, called the spike protein. This stimulates the body to make antibodies that target the protein, as well as triggering other immune responses. For decades, mRNA vaccines were considered unfeasible because the injection of mRNA into the body triggered an immune reaction that immediately broke down the mRNA. In the mid-2000s, working at UPenn, Karikó and Weissman demonstrated that swapping one type of molecule in mRNA, called uridine, with a similar one called pseudouridine bypasses the cells’ innate immune defences1. “I’m delighted to see them recognized,” says Robin Shattock, a vaccine scientist at Imperial College London, who has worked on mRNA vaccines. “Their contribution was really fundamental in the success of the COVID-19 vaccines, and I think will underlie RNA technology for some time to come.” “They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it,” said John Tregoning, a vaccine immunologist at Imperial College London, in a press statement for the UK Science Media Centre. “This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA.” “This discovery has opened a new chapter for medicine,” said Nobel committee member Qiang Pan Hammarström, an immunologist at the Karolinska Institute in Stockholm, at a press conference after the prize announcement. “Investment in long-term basic research is very important.”

doi: https://doi.org/10.1038/d41586-023-03046-x

Today, the U.S. Food and Drug Administration took action approving and authorizing for emergency use updated COVID-19 vaccines formulated to more closely target currently circulating variants and to provide better protection against serious consequences of COVID-19, including hospitalization and death. Today’s actions relate to updated mRNA vaccines for 2023-2024 manufactured by ModernaTX Inc. and Pfizer Inc. Consistent with the totality of the evidence and input from the FDA’s expert advisors, these vaccines have been updated to include a monovalent (single) component that corresponds to the Omicron variant XBB.1.5.

What You Need to Know

• Individuals 5 years of age and older regardless of previous vaccination are eligible to receive a single dose of an updated mRNA COVID-19 vaccine at least 2 months since the last dose of any COVID-19 vaccine. 
• Individuals 6 months through 4 years of age who have previously been vaccinated against COVID-19 are eligible to receive one or two doses of an updated mRNA COVID-19 vaccine (timing and number of doses to administer depends on the previous COVID-19 vaccine received). 
• Unvaccinated individuals 6 months through 4 years of age are eligible to receive three doses of the updated authorized Pfizer-BioNTech COVID-19 Vaccine or two doses of the updated authorized Moderna COVID-19 Vaccine.
• The FDA is confident in the safety and effectiveness of these updated vaccines and the agency’s benefit-risk assessment demonstrates that the benefits of these vaccines for individuals 6 months of age and older outweigh their risks.
• Individuals who receive an updated mRNA COVID-19 vaccine may experience similar side effects as those reported by individuals who previously received mRNA COVID-19 vaccines as described in the respective prescribing information or fact sheets.
• The updated vaccines are expected to provide good protection against COVID-19 from the currently circulating variants. Barring the emergence of a markedly more virulent variant, the FDA anticipates that the composition of COVID-19 vaccines may need to be updated annually, as is done for the seasonal influenza vaccine. 
• The U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices will meet tomorrow (Sept. 12), to discuss clinical recommendations on who should receive an updated vaccine, as well as further considerations for specific populations such as immunocompromised and older individuals. 
• Manufacturers have publicly announced that the updated vaccines would be ready this fall, and the FDA anticipates that the updated vaccines will be available in the near future.