Virus World

Comparison of the immune response to four prominent COVID-19 vaccines is among the most thorough so far, authors say.  A rare head-to-head comparison shows that the COVID-19 vaccines made by Pfizer and Moderna outperform those from Johnson & Johnson and Novavax1. The data also provide a finely detailed picture of the immune protection that each vaccine offers — information that could be useful for designing future vaccines. The research was posted on the preprint server bioRxiv on 21 March. It has not yet been peer reviewed. The study assessed the 4 vaccines using 14 metrics, including levels of several types of immune cell such as T cells and B cells, as well as immune molecules called neutralizing antibodies. Such investigations are sorely needed to sort through the flood of COVID-19 vaccines in the research pipeline and on the market, researchers say. “It’s a really nice analysis by premier immunologists that builds upon what has been previously shown,” says Robert Seder, an immunologist at the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.  Previous comparisons of COVID-19 vaccines have often brought together data from different studies, which might have been conducted with slightly varying laboratory techniques. For the latest study, by contrast, researchers applied the same techniques across all the vaccines they investigated. “When you try to compare [vaccine data] between different papers, which is what many of us have been doing for over a year now, you get apples to oranges comparisons, and you can be way off,” says Shane Crotty, an immunologist at La Jolla Institute for Immunology in California and a co-author of the preprint. The four vaccines that Crotty and his co-authors examined fall into three classes. The jabs made by Moderna in Cambridge, Massachusetts, and by Pfizer in New York City and BioNTech in Mainz, Germany, are both based on messenger RNA. Johnson & Johnson (J&J) of New Brunswick, New Jersey, has produced a ‘viral vector’ vaccine that uses a harmless virus to deliver SARS-CoV-2 genetic material into host cells. The vaccine made by Novavax in Gaithersburg, Maryland, contains pieces of the SARS-CoV-2 spike protein.

Strengths and weaknesses

Antibody levels induced by two doses of Pfizer’s or Moderna’s mRNA vaccine tended to wane substantially over six months. By contrast, antibody levels from J&J’s one-shot vaccine were stable or even increased over time. But antibody levels measured six months after vaccination with the J&J jab were still lower than those observed six months after vaccination with an mRNA vaccine. Novavax’s two-shot regimen induced antibody responses on a par with those to the mRNA vaccines. However, after the Novavax jab, levels of CD8+ T cells, which destroy infected cells, were low to undetectable, whereas the other three vaccines performed well in this metric. These results generally support the findings of previous studies. But the latest research offers a more extensive analysis of the immune system’s response than do earlier studies, and uses an apples-to-apples approach. 

No losers

“This is not meant to proclaim winners and losers,” says study co-author Alessandro Sette, an immunologist at La Jolla. Instead, the study is meant to “provide a comprehensive evaluation of the different variables”, he says. Novavax has received authorization for its vaccine in 38 countries. The vaccines made by Moderna, Pfizer and J&J have all received wide authorization globally. One caveat is that the study looked at the effects of the Novavax jab in only 12 people. It examined the other three vaccines in 30 volunteers each. Seder notes that the analysis considers the effects of only a two-dose regimen of the mRNA vaccines. It does not consider the protection provided by boosters, because the authors began the work in late 2020, before a third shot was recommended by health authorities. Crotty, Sette and their colleagues are now conducting a similar head-to-head study that includes mRNA boosters.

Cited research available at bioRxiv (March 21, 2022):

https://doi.org/10.1101/2022.03.18.484953  

Through Operation Warp Speed, the U.S. has backed seven vaccine candidates with $11 billion, securing preorders for some 800 million doses. Scientists, drugmakers and governments are moving with unprecedented haste to deliver a vaccine to protect against the new coronavirus. The fastest of them have already delivered early data from human studies, and further results from others should come quickly as the year progresses. The goal, at least in the U.S., is to have a vaccine ready for use in some fashion by the end of the year, or early next. Doing so would be a scientific feat with few parallels. No vaccine has ever been developed so quickly, never mind manufactured for the world. Researchers' success or failure could determine whether the virus becomes endemic, recurring in countries around the world year after year, or is ultimately checked.  With the health of their citizens at stake, governments are investing enormous sums of money into vaccine research and development, and to prepare for manufacturing and distributing what will likely need to be hundreds of millions of doses necessary to keep infection at bay.

The companies hope to earn the trust of the public and of scientists who have clamored for details of the studies.  Two drug companies that are leading the race to develop coronavirus vaccines bowed to public pressure on Thursday, abandoning their traditional secrecy and releasing comprehensive road maps of how they are evaluating their vaccines. The companies, Moderna and Pfizer, revealed details about how participants are being selected and monitored, the conditions under which the trials could be stopped early if there were problems, and the evidence researchers will use to determine whether people who got the vaccines were protected from Covid-1. Moderna’s study will involve 30,000 participants, and Pfizer’s 44,000.  Companies typically share these documents after their studies are complete. The disclosures while the trials are still underway, a rare move, are aimed at addressing growing suspicion among Americans that President Trump’s drive to produce a vaccine before the election on Nov. 3 could result in a product that was unsafe.  The plan released by Moderna on Thursday morning included a likely timetable that could reach into next year for determining whether its vaccine works. It does not jibe with the president’s optimistic predictions of a vaccine widely available to the public in October.

Pfizer’s plan does not appear to estimate when its results could be available. Its chief executive has said repeatedly that the company hopes to have an answer as early as October. Moderna has said only that it could have a result before the end of the year. Moderna’s 135-page plan, or protocol, indicated that the company’s first analysis of early trial data might not be conducted until late December, though company officials now say they expect the initial analysis in November. In any case, there may not be enough information then to determine whether the vaccine works, and the final analysis might not take place until months later, heading into the spring of next year. Moderna’s timeline meshes with the cautionary estimates from many researchers, including Dr. Robert R. Redfield, the director of the Centers for Disease Control and Prevention, who told senators on Wednesday that a vaccine would not be widely available until the middle of next year. Hours later, Mr. Trump sharply contradicted him, making unsubstantiated projections that a vaccine could become widely available weeks from now. On Wednesday, Joseph R. Biden Jr., the Democratic presidential nominee, said in Wilmington, Del., that the process used to evaluate and approve a vaccine would have to be “totally transparent” to win public confidence. He has said that Mr. Trump’s calls for companies and regulators to speed the process have shaken the public’s faith in vaccines and that politics has no place in vaccine development. Researchers in particular have been urging vaccine makers to share the detailed blueprints of their studies so that outside experts can evaluate them. At least one expert, after reading the plans, has already raised questions about the way the trials were designed. “I want to acknowledge a good deed done,” said Peter Doshi, who is on the faculty at the University of Maryland School of Pharmacy in Baltimore and an editor with The BMJ, a medical journal. He previously requested the plans from Moderna and Pfizer. “They have opened up, for the first time, the ability for researchers not involved in the trial to form their own independent judgment about the design of this study.”

Until now, none of the nine companies that are testing vaccines in large clinical trials had released this level of detail. Moderna, AstraZeneca and Pfizer, which is collaborating with the German company BioNTech, are among the front-runners in the global race to produce a vaccine to fight the pandemic. A spokeswoman for AstraZeneca said the company intended to publish its protocol shortly. Novavax, which is expected to start a large, advanced clinical trial later this year, also did not comment. Johnson & Johnson, which has said it plans to begin a large trial this month, said it would have “more information to share” when the trial starts.AstraZeneca’s trial was stopped temporarily because of serious illness in a participant. It has resumed in Britain and Brazil, but not in the United States. Earlier studies of both vaccines in small numbers of people found that after the second shot, they developed so-called neutralizing antibodies, which can inactivate the virus in lab tests. The vaccines also produced a favorable response involving T-cells, another part of the immune system...

Although none of the coronavirus vaccines under development has proved its efficacy yet in clinical trials, at least 5.7 billion doses have been pre-ordered  around the world. First shipments of a COVID-19 vaccine created by Western laboratories have often been snapped up by the United States. Five vaccines — three Western and two Chinese — are in Phase 3 efficacy trials involving thousands of people. In a surprise announcement, Russian President Vladimir Putin claimed Tuesday that a vaccine dubbed Sputnik V — after the Soviet satellite — conferred “sustainable immunity” against the novel coronavirus. As research laboratories around the world race to develop a vaccine, manufacturers have received financing to help them prepare to have millions of doses ready to administer in 2021 or even before the end of the year.

Oxford University, working with the Swedish-British pharmaceutical group AstraZeneca, hopes to have results by September, while the US biotech company Moderna, partnering with the U.S. National Institutes of Health (NIH), is aiming for the end of the year, possibly November. U.S. President Donald Trump has launched “Operation Warp Speed” in a bid to develop, manufacture and distribute a COVID-19 vaccine to all Americans by January 2021. Hundreds of millions of dollars have been directed to vaccine developers, including nearly $500 million to Johnson & Johnson at the end of March. The United States has allocated funding to more companies than any other nation in the hope that one of them will come up with the vaccine to counter the highly contagious virus. So far, Washington has handed out at a total of at least $9.4 billion to seven vaccine developers and signed manufacturing contracts with five of them to provide 700 million doses. The companies involved are: Johnson & Johnson, Moderna, Oxford/AztraZeneca, Novavax, Pfizer/BioNTech, Sanofi/GSK, Merck Sharp and Dohme.  Two vaccine developers — Oxford/AztraZeneca and Sanofi/GSK — have signed or are in advanced negotiations with the European Commission to provide a combined 700 million vaccine doses. Britain, because of Brexit, is negotiating a separate pre-order of 250 million doses from four developers.  Japan is counting on 490 million doses from three suppliers, including 250 million from Novavax of the United States. Pharmaceutical giant Takeda bought the rights to a Novavax vaccine for Japan, which has funded the research. It would be produced locally.

Brazil chose a similar model, ordering 100 million doses from AstraZeneca and partnering with China’s Sinovac to produce 120 millions of CoronaVac, which is already undergoing testing with Brazilians. Clinical tests of two Chinese vaccine candidates — Sinovac and Sinopharm — are well underway but only a few international partnerships have been announced, the one with Brazil and a possible one with Indonesia. Russia said 20 nations have pre-ordered 1 billion doses of Sputnik V and that with foreign partners it would be able to produce 500 million doses a year in five countries. The Coalition for Epidemic Preparedness Innovations, launched in 2017 by Norway, India, the Bill and Melinda Gates Foundation and the Wellcome Trust, seeks to ensure that there is “equitable access” to future vaccines. It has pre-ordered 300 million doses from AstraZeneca for dozens of developing countries in a partnership with The Vaccine Alliance. Billions of doses would be produced for Asia and elsewhere by the giant Serum Institute of India (SII), the largest vaccine producer in the world. Novavax and AstraZeneca have separately signed agreements with SII to produce a billion doses each for India and low- and middle-income countries on the condition that they prove their efficacy in clinical trials.