Fourth Covid jab can give higher immunity than initial booster, study finds UK-based team finds antibodies peaked higher after fourth jab given after gap of more than six months than after third https://www.theguardian.com/society...her-immunity-than-initial-booster-study-finds A fourth dose of a Covid vaccine can ramp up the body’s immune defences beyond the peak achieved after a third dose, research suggests. A second booster – often a fourth dose of a Covid vaccine – is currently offered in the UK to those aged 75 or over, people living in care homes for older people, and those over the age of 12 who are immunosuppressed. Now researchers say they have found a fourth dose can rescue immune responses that have waned since a third jab. “We’ve demonstrated a fourth dose of Covid-19 vaccines can produce a substantial boost to both the antibody and cellular immunity when you give them more than six months after the third dose,” said Prof Saul Faust, who led the trial and is director of the NIHR Southampton clinical research facility. Writing in the Lancet Infectious Diseases, researchers involved in the UK-based Cov-Boost trial report how they measured immune responses in 166 participants who received a fourth Covid jab on average seven months after having had a Pfizer/BioNTech jab as their third dose. All participants had initially had either two doses of the Pfizer/BioNTech jab or two doses of the Oxford/AstraZeneca vaccine. Half were randomly allocated to receive a full dose of the Pfizer/BioNTech Covid jab as their fourth vaccination, while the others were given half a dose of the Moderna jab. No serious adverse events were linked to the vaccines. The team analysed data from 133 participants, finding that 14 days after receiving the fourth jab, there was a 1.6-fold increase in antibodies among those who received the Pfizer/BioNTech vaccine, and a more than twofold increase among those who received the half-dose Moderna jab, compared with 28 days after the third dose, when antibody levels were still at their peak. Increases were seen for those over and below 70 years of age. In addition, levels of antibodies and T-cells increased substantially between the day before the fourth vaccination and 14 days after for both types of fourth jab. “Our results for immunogenicity are also consistent with the little observational evidence on vaccine effectiveness available from Israel, which indicates increased protection against symptomatic infection and severe illness from a fourth-dose booster,” the team write. Faust added that those who had little waning of their immune responses before their fourth dose gained only a limited increase in their immune responses as a result of the booster – with similar findings for others who had a recent history of a Covid infection. “That indicates there may be a ceiling, a maximum antibody level with the T-cell response effects,” he said. Faust said it was up to the UK’s Joint Committee on Vaccination and Immunisation to decide whether a second booster should be offered more widely. Some experts have suggested in the current circumstances those yet to reach middle age might never be offered another Covid jab. But Prof Danny Altmann, an immunologist at Imperial College London, said Omicron still posed a serious threat, adding that the new study demonstrated the added value of a fourth dose. “Just because our first-generation vaccines wane rapidly and offer rather permeable protection nowadays, does not suggest we should give up and have no further boosters,” he said. “On the contrary, [given] many of us, even with high apparent antibody levels, actually show [very little] protective neutralisation of Omicron, there is all the more urgency to use [fourth] doses – in all age groups – to boost levels back up into the protective range.”
FDA authorizes Pfizer Covid-19 booster shots for children ages 5 to 11 https://www.cnn.com/2022/05/17/health/fda-covid-booster-kids-5-11/index.html The US Food and Drug Administration has granted emergency use authorization for a booster dose of Pfizer/BioNTech's Covid-19 vaccine for children ages 5 to 11 at least five months after completion of the primary vaccine series. Pfizer requested this EUA at the end of April, citing company data that showed that a third vaccine dose raised Omicron-fighting antibodies by 36 times in this age group. "While it has largely been the case that COVID-19 tends to be less severe in children than adults, the omicron wave has seen more kids getting sick with the disease and being hospitalized, and children may also experience longer term effects, even following initially mild disease," FDA Commissioner Dr. Robert Califf said in a news release Tuesday. "The FDA is authorizing the use of a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine for children 5 through 11 years of age to provide continued protection against COVID-19. Studies from the New York State Department of Health and the US Centers for Disease Control and Prevention found that the effectiveness of two doses of Pfizer's vaccine for children ages 5 to 12 dropped substantially during the Omicron surge, falling from 68% to about 12% against infection. However, two doses continued to provide protection against more severe illness resulting in urgent care or hospitalizations. Public health officials have urged Americans to stay up to date with their Covid-19 vaccinations, including all recommended booster doses, as the best way to protect themselves and the people around them. A recent CNN analysis of CDC data showed that for those who were fully vaccinated and boosted in February, the risk of dying from Covid-19 was 20 times lower than it was for unvaccinated people 12 and older. The CDC's Advisory Committee on Immunization Practices will meet Thursday to discuss Covid-19 vaccine boosters. Though the agenda for the meeting has not been posted, a vote is scheduled, according to the Federal Register. Tuesday's decision means anyone 5 and older is now eligible for at least one booster dose. Those who are 50 and older and people 12 and older who have certain kinds of immunocompromise are eligible for two booster doses. Moderna has also requested FDA authorization for a second Covid-19 booster shot for everyone 18 and older, but a decision has yet to be made regarding that request. This is a developing story and will be updated.
C.D.C. advisers recommended Pfizer vaccine boosters for children 5 to 11, who will be eligible immediately upon the C.D.C. director’s sign-off. The experts said a booster shot of the vaccine would offer children an extra layer of protection at a time when infections and hospitalizations are once again rising nationwide. Boosters were recommended for adults in November and for children 12 and older in January. Thursday, May 19, 2022 3:55 PM ET https://www.nytimes.com/2022/05/19/health/pfizer-vaccine-booster-kids.html
Work on a longer-lasting universal coronavirus vaccine is still moving forward. But there is a long way to go. The quest for longer-lasting Covid-19 vaccines https://www.cnn.com/2022/05/20/health/mrna-vaccine-technology-covid-19-durability/index.html As waves of new coronavirus variants circulate the globe, one thing has become clear: human immunity against the virus fades over time. To maintain durable protection against the virus that causes Covid-19, scientists are working around the clock to develop next-generation vaccines. But some of the nuances around why and how immunity against Covid-19 fades remain a mystery. The steepest drops in immunity -- which come about four to five months after vaccination and up to eight months after infection, but can vary -- are against Covid-19 symptoms, getting infected and getting sick. Protection against severe outcomes, hospitalization and death remains much higher for a longer period of time, but even this decays to some degree, especially for the elderly and those with compromised immune function. Since the early days of the pandemic, scientists have known that the coronavirus carries a structure called the spike protein, and it uses this crown of spikes to get into the cells it attacks. Our Covid-19 vaccines create antibodies to these spike proteins that bind to the docking sites on the virus, blocking them from infecting our cells. Yet our safety net against the virus is wearing thin, in part because the virus is changing like a fugitive donning a disguise -- picking up mutations that change the shape of its spikes in ways that make it less recognizable to our immune system. But there's another piece of the immunity puzzle that scientists are urgently trying to solve, and that is whether some of this drop off in our protection may be a result of the mRNA technology used to build some Covid-19 vaccines, such as those developed by Moderna and Pfizer/BioNTech, which were the first in the world to use this platform. "Some vaccine platforms give a very high degree of protection but the durability isn't very long," said Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases in an interview with CNN. Fauci said that the mRNA platform may be one of those. In clinical trials, the new mRNA vaccines have proven to be astonishingly good at protecting people against illness, hospitalizations and deaths, at least in the short term. Fauci said mRNA vaccines have other advantages, too. It's relatively fast and easy to redesign them to better protect against new variants, for example. "We got a really great platform with mRNA," Fauci said. "But let's try to be better. Because our experience, maybe it's peculiar to coronavirus, but I doubt it, is that the durability of the response you can be better on." 'We've got to get better platforms' To be fair, Fauci said we won't know how long immunity induced by these kinds of vaccines may last until mRNA is used to make vaccines against a different type of pathogen, perhaps one that doesn't change as much as SARS-CoV-2, the virus that causes Covid-19. Definitive answers may be years away. In the meantime, he said, we can't wait. We need to improve the vaccines if we're going to keep Covid-19 at bay. "We have very good vaccines, but we've got to get better platforms and immunogens, maybe with adjuvants that allow us to have a greater durability of protection," Fauci said. Adjuvants are extra ingredients in vaccines that help them work better. Other experts agree. Deepta Bhattacharya heads a lab at the University of Arizona where he studies the lifespan of plasma cells, a type of long-lasting cell that makes protective antibodies. He's also interested in how various vaccine technologies influence the persistence of these cells in our bodies. What we can tell after more than a year of experience with the mRNA vaccines is that their protection starts high but seems to fade more quickly than the immunity that remains after a Covid-19 infection, according to Bhattacharya. "There have been a few side-by-side studies that have compared the mRNA vaccines to infection-induced immunity, and it seems like it slips a little bit faster than that," Bhattacharya said. Though he cautioned that protection after an infection varies greatly from person to person just because everyone's immune system is a little different. There's no good way to know, right now, how well any particular person's immune system responds to a vaccine, which is why it's important to be vaccinated, even if you've already had Covid-19. He added that when comparing the performance of the mRNA vaccines to adenoviral vector vaccines, such as those developed by AstraZeneca and Johnson & Johnson, people initially make a lot more antibodies after vaccination with an mRNA vaccine, but these levels seem to fall pretty steeply by around the six-month mark. Adenovirus vaccines use another virus as a Trojan horse to sneak instructions for making the spike proteins into cells. With the adenoviral vector vaccines, antibody levels don't seem to climb as high initially as they do with mRNA vaccines, but they do seem to persist for longer periods at these lower levels, pointing to some difference in the body's response to them that we don't fully understand. In a large study of more than 35,000 health care workers in the United Kingdom, compared to those who were unvaccinated, those who had two doses of the Pfizer/BioNTech mRNA vaccine were about 85% less likely to get a Covid-19 infection, through about two and a half months after their second dose. But by six and a half months, that protection against infection had fallen to about 51%. The follow up period for the study was between December 7, 2020, when the vaccines were first given to healthcare workers in the UK to Sept. 21, 2021, so it doesn't include Omicron infections. Health care workers with two doses of the Astrazeneca adenoviral vector vaccine were about 58% less likely to get a Covid-19 infection compared to those who were unvaccinated, through about two and a half months after vaccination, but the effectiveness of that vaccine appeared to increase over time, cutting the risk of infection by more than 70% about seven months after a second dose. Health care workers who caught a Covid-19 infection, most of them happening in March 2020, before the era of vaccines, were initially about 86% less likely to be reinfected, and that protection lasted up to a year. After a year, it dropped to about 69% in workers who were unvaccinated, which was still better than the protection from mRNA vaccines alone. Workers who had caught Covid-19 and went on to be vaccinated had the best protection of all, more than a 90% lower risk of getting Covid-19 again, and that combined protection stayed high for the duration of the study, which was more than 9 months. This evidence and other studies, said Bhattachayra, suggests our immunity against Covid can be tweaked to make it last longer. "I do think it's fair to ask more of our vaccines and that they sort of maintain that protection for longer," Bhattachayra said. "I think there's still very clearly room for improvement because there are certain vaccines that do better" in terms of their durability, he said. "There's no question about that." Other vaccines have needed improvements to help them last longer Starting at two months of age, doctors recommend that babies get a vaccine against Haemophilus influenzae, or Hib, a common bacteria that can cause serious infections if it invades the lungs, blood or brain. These bacteria are coated with chains of sugars, or polysaccharides, that help mask them to our immune systems. In the 1980s, scientists figured out that you could use those sugar chains to build a vaccine to protect children from serious infections. "The initial Hib vaccine was a polysaccharide vaccine, but it did not induce long-lived antibody levels, so we don't even use it now," said Dr. Gregory Poland, an infectious disease expert who studies how the immune system responds to vaccines at the Mayo Clinic in Minnesota. Today's Hib vaccine still contains the sugar chains, but they are linked to protein pieces that stimulate a different part of the immune system to better remember the bacteria. It's called a protein conjugate vaccine. Another example of a vaccine that didn't ultimately provide long-lasting immunity was the pneumococcal vaccine for pneumonia. It, too, started life as a polysaccharide vaccine, but was changed to a protein conjugate after researchers determined that change could extend its protection. Some vaccines use extra ingredients, called adjuvants, to hyperstimulate the immune system, which increases the strength of the protection people get from them. These kinds of vaccines are often used for older adults and others whose immune systems need an extra kick in the pants, so to speak, to work. Certain vaccines inherently do this, just because of the way they are designed, Fauci said, and the nanoparticles being built into some experimental vaccines are an example of this. Fauci added that he's not sure why the immune response triggered by mRNA vaccines may not be longer lasting. He has some theories, though. One of the early failures in developing the mRNA technology was that when the chains of molecules called nucleic acids were injected into animals, they triggered an immune response too quickly. The animals got sick and their immune systems destroyed these chains -- or instructions -- before cells could read them and build the proteins they coded for. One breakthrough in turning these instructions into vaccines was that the scientists who developed them figured out how to make a chemical change to the mRNA to hide it from the immune system until it could get inside cells, thus, reducing the risk of getting sick. "They modified the molecule to remove the inflammatory aspect of it, to allow it to be used as a vaccine, that possibly--and I underlined 15 times, possibly--could be reason why," Fauci said. "Maybe if we use this mRNA, but add a different adjuvant with it, you might get a really good response, the best of both worlds, you might get the real advantage of an mRNA together with a bit more durability, if you add to it an adjuvant as opposed to having the molecule itself be inherently adjuvant." Bhattachyra has another theory about why the mRNA platform may not be lasting as long. He said these vaccines instruct cells to build spike proteins from the virus and then display them on their surfaces, where they can be seen by the immune system. But cells are giant compared to viruses -- about 100 times larger, he said, and viruses pack about 25 spike protein trimers onto their smaller surface, making them pretty densely packed. A trimer is a type of chemical compound or molecule that has three pieces. "I don't know what the density of spike proteins is on a cell; it may not be as high as what it is on a virus, for instance," Bhattachyra said. No one really knows what the spike-expressing cells look like and how closely they resemble the virus they're targeting. "It could be that the spacing is pretty infrequent and you're just not getting the level of activation that you would want," he said, adding "that's pure speculation." Planning for the future The United States is at a point in the pandemic now where health officials are grappling with the fact that to maintain immunity against Covid-19 in the community, the nation will either need to administer booster shots on a regular -- or possibly annual -- basis, or will need to rollout an entirely new vaccine altogether. All vaccines have strengths and weaknesses -- but some of the nation's leading vaccine experts argue that more research is needed into the durability of the currently used Covid-19 vaccines as a potential weakness, as vaccine-induced immunity can decline within four to six months. For instance, during the recent Omicron wave in the United States, the protection that vaccine boosters provide fell more than four months later from more than 90% to around 66% for protection against emergency room visits for Covid-19 and 78% against hospitalizations, Dr. Peter Hotez, CNN medical analyst and virologist and co-director of Texas Children's Hospital Center for Vaccine Development, told CNN. "The big unknown is this: How much of that decline is due to something quirky because of the Omicron variant? Or, is this a weakness in the technology and it's not holding up? And it's very hard to sort out," Hotez said. "All vaccines have strengths and weaknesses, and it may be that for mRNA that it does not produce durable protection. It could be that you go in, use mRNA vaccines to rapidly immunize a population, stabilize it, but then over time, you're going to have to come in with a heterologous boost that's a different technology." Hotez, whose lab has developed a Covid-19 vaccine called Corbevax, said that the White House should convene vaccine experts in a special meeting to "pin down" whether the technology has that weakness and what it means for future strategies. In an effort to find the answer to maintaining durable protection against Covid-19, several research groups are working to develop so-called "next-generation vaccines" that aim to induce longer-lasting protection and even "pan-coronavirus" vaccines, ones that offer protection against multiple variants of the coronavirus that causes Covid-19. "How do you make the Covid responses induced by vaccines more long-lasting? How do you make this process of inducing long-lived plasma cells more efficient? That's the name of the game right now," said Dr. Barton Haynes, director of the Duke Human Vaccine Institute. "There are a number of groups working on mRNAs for the next generation vaccines full well aware that, for those vaccines to be more long-lasting, breakthroughs need to be made," he said. Haynes is also working on a different type of vaccine — a nanoparticle containing fragments of the coronavirus' spike protein. This vaccine also includes an ingredient that enhances the immune response, known as an adjuvant. A key long-term goal is to create a more universal vaccine that can work against new variants of this coronavirus, plus others that cause common colds and even ones we haven't identified yet. The protein-based vaccine is one of several that target conserved sites on the spike protein -- ones that don't mutate, lest they hinder their ability to infect human cells. And Haynes said research in monkeys appears to show it does a better job than mRNA vaccines at generating those kinds of antibodies that provide broader coverage, as well. This may be due to a combination of how well the adjuvant works to stimulate the immune system, and perhaps the design of the nanoparticle itself, which almost looks like a virus, he added. Regardless of the vaccine platform, "we're all going after formulations that will induce durable, long-lasting antibody and other types of T-cell immunity." So far during the coronavirus pandemic, vaccine protection has been measured by the presence of antibodies in the blood. Antibodies are proteins made by the immune system to help fight infections. But there is more to the human immune system than just antibodies. The immune system involves a host of players, including B cells, which produce antibodies, and T cells, which target infected cells during an infection -- and T cells are often part of emerging discussions around vaccine durability. A study published in the journal Cell in January showed just how much of a role the other parts of the immune system play in the durability of protection following Covid-19 vaccination. The study found that, among 96 vaccinated adults, even though antibody levels decreased against coronavirus variants, the T cells induced by various types of Covid-19 vaccines -- the Moderna, Pfizer/BioNTech, Johnson & Johnson and Novavax vaccines -- were able to recognize coronavirus variants, including Omicron, even though the vaccines were developed based on the original coronavirus. "The important thing for our study was we collected all those samples at the same place with the same techniques and ran all the experiments head-to-head so it was really a fair head-to-head test," said Shane Crotty, virologist and professor at La Jolla Institute for Immunology, who was an author of the study. Plus, those vaccines were developed using different technologies. Moderna and Pfizer/BioNTech are mRNA vaccines. Johnson & Johnson is a viral vector vaccine. Novavax, which is not yet authorized for emergency use in the United States, is a protein-based vaccine. "The mRNA vaccines, both Moderna and Pfizer, generated these four categories: antibodies, memory B cells, helper T cells and killer T cells. Overall, the mRNA vaccines generated the best of all four of those," Crotty said, adding that among people who were vaccinated with Johnson & Johnson, generally there appeared to be less of all four and Novavax appeared to generate somewhat less memory B cells and significantly less killer T cells. "So, there were some different mixes there," Crotty said. "Our immunological data are generally consistent with the vaccine efficacy data that's out there from the clinical trials and real-world studies that in general, the mRNA vaccines are better than J&J in terms of protection from infection but also protection from hospitalization, with Novavax being somewhere in between, but doing quite well." Many experts seem to agree that discussions around future Covid-19 vaccination strategies should hinge on what exactly the goal of the vaccines are -- to prevent the spread of the coronavirus or to keep people out of the hospital. "So if your goal is to prevent any new infections in our society, then yeah, we're going to have to keep boosting, because our antibody levels are going to decline -- no matter what kind of vaccine we get," Jen Gommerman, professor and acting chair in the Department of Immunology at the University of Toronto, told CNN. She added that, among the vaccines authorized for emergency use in the United States, the rate of decline for the Johnson & Johnson vaccine is a bit lower than for Moderna's and Pfizer/BioNTech's mRNA vaccines. However, the peak level of protection that the Johnson & Johnson vaccine providers is lower than the peak for the mRNA vaccines. "So, the raw amount of antibody in our serum is going down to a level where you will be susceptible to infection and the only way to get those antibodies back up quickly, is to either get infected or get boosted," Gommerman said. "However, if we consider efficacy against hospitalization and severe disease, the data coming out show that three doses of the mRNA vaccine confirm excellent protection against hospitalization, ventilation and death," she said. "For me, personally, I would get a fourth dose if I knew it would serve public health reasons. But for me personally, I don't feel I need a fourth dose to protect myself against severe disease, hospitalization or death." 'Many more questions still need answers' There are still many questions left to answer about Covid-19 vaccines and immunology, John Wherry, director of the Institute for Immunology at the University of Pennsylvania's Perelman School of Medicine, wrote in an email to CNN. Those questions include: How long do memory B cells and memory T cells last? How do the vaccines containing the original coronavirus, identified in Wuhan, China, induce effective immune memory against all the variants so far? What immune mechanisms provide protection from infection versus protection from severe disease, hospitalization and death? Why do different people respond differently to these vaccines? "These and many more questions still need answers if we are going to use this platform most effectively," Wherry wrote. Such questions also need answers in the context of vaccine durability, especially as the durability of protection and the durability of immune responses themselves are related -- but not the same, according to Wherry. For the mRNA vaccines, "durability of protection is on par with other vaccine types from the analyses we have seen on the adenoviral platforms versus mRNA. Durability of immune responses -- it's been difficult to do really precise comparative studies longitudinally over a time frame relevant to answer this question," Wherry wrote in his email. After all, the vaccines have only been around for about a year and a half, and answering questions around durability precisely can be founded by the introduction of booster shots and the incidence of breakthrough infections. "This later point is relevant because it dramatically influences the durability to immune responses over time," Wherry wrote about breakthrough infections. "The bottom line is that the data so far look very promising for durability of immune responses and protection from severe disease. Protection from mild disease is much more difficult for this virus and might only be achieved transiently when antibody levels are extremely high."
Three-dose Covid-19 vaccine produces strong immune response in children ages 6 months to 5 years, Pfizer and BioNTech say https://www.cnn.com/2022/05/23/health/pfizer-covid-vaccine-results-young-children/index.html Three child-size doses of the Pfizer/BioNTech Covid-19 vaccine appeared to be safe and showed a strong immune response in children ages 6 months to 5 years, the companies said Monday. The vaccine makers said they will finish submitting the trial data to the US Food and Drug Administration this week. The Phase 2/3 trial included 1,678 children who received a third dose during the period when the Omicron coronavirus variant dominated. Antibody levels tested one month after the third dose showed the vaccine produced a similar immune response as two doses in 16-to-25 year-olds, the companies said in a news release. The data has not yet been peer-reviewed or published. Midtrial results found vaccine efficacy of 80.3% against symptomatic Covid-19 in this youngest age group. The companies identified 10 symptomatic cases at least seven days after the third dose. However, the efficacy rate won't be finalized until at least 21 symptomatic cases are found in the vaccine group and then compared with the number of symptomatic cases in the placebo group. The companies said three child-size doses for this youngest age group were "well-tolerated" and no new safety signals were identified. "These topline safety, immunogenicity and efficacy data are encouraging, and we look forward to soon completing our submissions to regulators globally with the hope of making this vaccine available to younger children as quickly as possible, subject to regulatory authorization," Pfizer Chairman and CEO Albert Bourla said in a statement. The vaccines for this youngest age group are smaller than those used in older age groups. People age 12 and older receive two doses of a 30-microgram vaccine and children ages 5 to 12 receive two doses of a 10-microgram vaccine. Both age groups are eligible for booster doses. For children 6 months to 5 years, the Pfizer/BioNTech vaccine is three 3-microgram doses. The initial two doses were given three weeks apart, and the third dose was given at least two months after their second dose. Children younger than 5 are the only age group not yet eligible for vaccination against Covid-19. The vaccine for this age group was delayed when results of a two-dose series of the Pfizer/BioNTech vaccine didn't provide the expected level of protection. The companies said they would amend the trial to add a third dose. In February, the US Food and Drug Administration asked the companies to submit a request for emergency use authorization based on the two-dose data, but then postponed a meeting of the agency's vaccine advisory board so the third-dose data could be considered. The FDA's Vaccines and Related Biological Products Advisory Committee has tentative meetings scheduled for June 8, 21 and 22 to discuss emergency use authorizations updates that could make younger children eligible for vaccination with the Moderna or Pfizer/BioNTech vaccines. Moderna submitted its vaccine data for children 6 months through 5 years of age to the FDA in late April. Moderna's submission is based on two 25-microgram doses given 28 days apart.
Western nations quickly moved over to using mRNA vaccines which have perceived to be more effective and safe. While J&J and AstraZenenca had issues with blood clots in a very small number of people. What happened to all of those doses of AstraZeneca your ask? They have gone out all over the world. What happened to the AstraZeneca vaccine? Now rare in rich countries, it’s still saving lives around the world https://theconversation.com/what-ha...ts-still-saving-lives-around-the-world-181791 The AstraZeneca vaccine, developed in partnership with the University of Oxford, was one of the first vaccines available for use in the UK and around the world during the COVID pandemic. More than two billion doses have been distributed to at least 170 countries, with around 50 million doses administered in the UK. But most of those were first and second doses – only a little over 56,000 doses of AstraZeneca had been given as booster doses as of May 2022. The vast majority of third doses administered in the UK have been Pfizer (30.1 million doses) and Moderna (9.4 million). So despite being an excellent vaccine, the use of AstraZeneca in the UK has declined across the pandemic. It’s also not used much elsewhere in Europe, or in the US where it has yet to be approved. The reason for its limited use in high-income countries could be a combination of two factors. First, it’s likely that the mRNA vaccines (specifically those manufactured by Pfizer and Moderna) are perceived to be even more effective than AstraZeneca. And second, the vaccine’s reputation took a hit when some people who received this vaccine subsequently developed blood clots. On the first point, some research has indicated the mRNA vaccines offer slightly higher levels of protection against previously dominant variants, including delta. A 2022 study from the Netherlands that measured antibody levels against SARS-CoV-2 following vaccination showed Pfizer and Moderna performed better than the viral vector vaccines (including AstraZeneca). But one caveat here is that the participants who received the mRNA vaccines were much younger than the AstraZeneca recipients. Immune responses typically wane faster in older populations. The public fallout from the blood clot scares, associated with AstraZeneca but not with Pfizer or Moderna, also affected the vaccine’s rollout. The vaccine is still licensed for use in younger adults in the UK, who were deemed to be at higher risk of blood clots following the AstraZeneca vaccine. However, the UK’s Joint Committee on Vaccination and Immunisation recommended that people aged 39 and under should be offered an alternative to AstraZeneca where possible. These adverse events gained significant media coverage, and public confidence in the AstraZeneca vaccine was certainly knocked in the UK and beyond. For example, in April 2021, Denmark became the first European country to cease using the vaccine, with Norway following soon after. Around the same time, several Canadian provinces temporarily suspended the AstraZeneca vaccine for people under 55 as a precautionary measure. All of this came amid high levels of COVID in these countries and elsewhere, and at a time when global demand for COVID vaccines greatly outstripped supply. These somewhat kneejerk reactions made waves further afield. For example, research my colleagues and I conducted in Ghana highlighted how people had observed the responses in Europe and North America. The result was increased hesitancy towards the AstraZeneca vaccine. Despite all this, the UK’s Medicines and Healthcare products Regulatory Agency, the European Medicines Agency and the World Health Organization continued at all times to recommend the vaccine, based on its safety and effectiveness record. An important vaccine for the developing world The proportion of the Ghanaian population that has received one or more doses of any COVID vaccine is just over 30%. Our 2022 research in Ghana indicates that vaccine hesitancy rates among those currently unvaccinated ranges between 30%-50%, depending on the population surveyed. An April 2022 briefing by the Ghana Health Service (not published online) indicated that 43% of the 28 million doses received in Ghana have been AstraZeneca. Of the vaccines administered in March 2022, 57% were AstraZeneca. Among the reasons for a preference for AstraZeneca, there will be considerations around supply, cost and logistical issues. For example, the vaccine requires only regular refrigerator storage, compared with the mRNA vaccines which need to be frozen. For these reasons the AstraZeneca vaccine is vital for Ghana, along with many other lower-income countries. High local and global confidence is essential to ensure a successful vaccination campaign with high uptake. The UK and many other high-income countries are likely to continue predominantly using mRNA COVID vaccines. However, much of the knowledge we have around “which vaccine is better” relates to previous variants rather than omicron. As the virus continues to evolve, so must the evidence base. There is an increasing body of evidence that “mixing and matching” vaccine types is safe and effective, and may even generate stronger or broader immune responses over time. In this light, there could be a role for AstraZeneca or other vaccines such as Novavax, alongside mRNA vaccines. In the longer term, we need a vaccine that can protect against multiple variants or even all coronaviruses. For many high-income countries in 2022, the mRNA vaccines are the vaccine of choice, rather than AstraZeneca. The mRNA vaccines are also being manufactured in sufficiently large volumes to make supply much less of an issue than it was earlier in the pandemic. These are all important factors for national decision-makers. However, it’s important to emphasise that the AstraZeneca vaccine is a safe and effective product, and remains a vital tool to underpin the global response to the pandemic.