In a new review, some FDA scientists & others say boosters aren't needed for the general population

[Celerity]

https://www.nytimes.com/2021/09/13/health/covid-vaccine-booster-lancet.html

None of the data on coronavirus vaccines so far provides credible evidence in support of boosters for the general population, according to a review published on Monday by an international group of scientists, including some at the Food and Drug Administration and the World Health Organization.

The 18 authors include Dr. Philip Krause and Dr. Marion Gruber, F.D.A. scientists who announced last month that they will be leaving the agency, at least in part because they disagreed with the Biden administration’s push for boosters before federal scientists could review the evidence and make recommendations. The Biden administration has proposed administering vaccine boosters eight months after the initial shots. But many scientists have opposed the plan, saying the vaccines continue to be powerfully protective against severe illness and hospitalization. A committee of advisers to the F.D.A. is scheduled to meet on Friday to review the data.

In the new review, published in The Lancet, experts said that whatever advantage boosters provide would not outweigh the benefit of using those doses to protect the billions of people who remain unvaccinated worldwide. Boosters may be useful in some people with weak immune systems, they said, but are not yet needed for the general population. Several studies published by the Centers for Disease Control and Prevention, including three on Friday, suggest that while efficacy against infection with the Delta variant seems to wane slightly over time, the vaccines hold steady against severe illness in all age groups. Only in older adults over 75 do the vaccines show some weakening in protection against hospitalization.

Immunity conferred by vaccines relies on protection both from antibodies and from immune cells. Although the levels of antibodies may wane over time — and raise the risk of infection — the body’s memory of the virus is long-lived. The vaccines are slightly less effective against infection with the Delta variant than with the Alpha variant, but the virus has not yet evolved to evade the sustained responses from immune cells, the experts said. Boosters may eventually be needed even for the general population if a variant emerges that sidesteps the immune response. The experts cautioned that promoting boosters before they are needed, as well as any reports of side effects from booster shots such as heart problems or Guillain-Barre syndrome, may undermine confidence in the primary vaccination. Data from Israel suggest that booster doses enhance protection against infection. But that evidence was collected just a week or so after the third dose and may not hold up over time, the experts said.

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[Celerity]

1. A more detailed article from the NYT, plus a section of The Lancet article

In Review, Top F.D.A. Scientists Question Imminent Need for Booster Shots

An article, written with other vaccine experts, put the regulators at odds with key federal health officials, including Dr. Anthony S. Fauci.

https://www.nytimes.com/2021/09/13/health/fda-coronavirus-booster-shots.html

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But in the new review, Dr. Krause, Dr. Gruber and other vaccine experts said that more time and public discussion, and better studies, were needed to determine if boosters were needed for the general population. They also said that whatever advantage the shots might provide would not outweigh the benefit of using them to protect the billions of people who remain unvaccinated worldwide. The World Health Organization has asked wealthy countries to hold off on administering extra shots to healthy patients until at least the end of the year as a way of enabling every country to vaccinate at least 40 percent of its population. Every unvaccinated person provides an opportunity for the virus to morph into new, potentially dangerous, variants, scientists have warned. The review authors did, however, say that extra shots might be useful for some people with weak immune systems — a step the F.D.A. already authorized. “As more information becomes available, it may first provide evidence that boosting is needed in some subpopulations,” they wrote. “However, these high-stakes decisions should be based on peer-reviewed and publicly available data and robust international scientific discussion.”

They were largely dismissive of the Israeli data and other studies that some health officials have said make the case for imminent extra shots. They said some Israeli evidence was collected just a week or so after the third dose and might not hold up over time, and that “a very short-term protective effect would not necessarily imply worthwhile long-term benefit.” They also said that a reduction in vaccine efficacy against mild cases of Covid-19 did not necessarily mean there would be a drop in efficacy against severe disease. “To date, none of these studies has provided credible evidence of substantially declining protection against severe disease,” they wrote, “even when there appear to be declines over time in vaccine efficacy against symptomatic disease.” The authors also said that countries with a lot of vaccinated people would inevitably see some breakthrough cases, especially if the vaccinated start taking more risks.

Several studies published by the C.D.C., including three on Friday, suggest that while efficacy against infection with the Delta variant seems to wane slightly over time, the vaccines hold steady against severe illness in almost all age groups. Only in adults over 75 do the vaccines show some weakening in protection against hospitalization. Immunity conferred by vaccines relies on protection both from antibodies and from immune cells. Although the levels of antibodies may wane and raise the risk of infection, the body’s memory of the virus is long-lived. The vaccines are slightly less effective against infection with the Delta variant than with the Alpha variant, but the virus has not evolved to evade the sustained responses from immune cells, the experts said. Boosters may eventually be needed even for the general population if a variant emerges that sidesteps the immune response, they added.

The experts cautioned that promoting boosters before they are needed, as well as any reports of booster side effects such as heart problems or Guillain-Barré syndrome, might undermine confidence in the primary vaccination. They wrote that because booster doses have been shown to induce strong responses, lower doses might be adequate and safer. They also emphasized that tweaking the vaccines to specifically protect against new variants, like Delta, might be the best and longest-lasting approach, in part because new variants would be likely to evolve from those in highest circulation. Moderna and Pfizer are both evaluating Delta-specific booster shots. The F.D.A. is still gathering data on all three vaccines used in the United States, and it will be at least several weeks before regulators can decide whether people who received the Moderna or Johnson & Johnson vaccines might need another dose. Starting boosters for recipients of only one vaccine could confuse the public, the authors said. “Booster programs that affect some but not all vaccinees may be difficult to implement — so it will be important to base recommendations on complete data about all vaccines available in a country, to consider the logistics of vaccination, and to develop clear public health messaging before boosting is widely recommended,” the authors wrote.

https://www.thelancet.com/pb-assets/Lancet/pdfs/S0140673621020468.pdf

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The message that boosting might soon be needed, if not justified by robust data and analysis, could adversely affect confidence in vaccines and undermine messaging about the value of primary vaccination. Public health authorities should also carefully consider the consequences for primary vaccination campaigns of endorsing boosters only for selected vaccines. Booster programmes that affect some but not all vaccinees may be difficult to implement—so it will be important to base recommendations on complete data about all vaccines available in a country, to consider the logistics of vaccination, and to develop clear public health messaging before boosting is widely recommended.

If boosters (whether expressing original or variant antigens) are ultimately to be used, there will be a need to identify specific circumstances in which the direct and indirect benefits of doing so are, on balance, clearly beneficial. Additional research could help to define such circumstances. Furthermore, given the robust booster responses reported for some vaccines, adequate booster responses might be achievable at lower doses, potentially with reduced safety concerns. Given the data gaps, any wide deployment of boosters should be accompanied by a plan to gather reliable data about how well they are working and how safe they are. Their effectiveness and safety could, in some populations, be assessed most reliably during deployment via extremely large-scale randomisation, preferably of individuals rather than of groups.

Thus, any decisions about the need for boosting or timing of boosting should be based on careful analyses of adequately controlled clinical or epidemiological data, or both, indicating a persistent and meaningful reduction in severe disease, with a benefit–risk evaluation that considers the number of severe cases that boosting would be expected to prevent, along with evidence about whether a specific boosting regimen is likely to be safe and effective against currently circulating variants. As more information becomes available, it may first provide evidence that boosting is needed in some subpopulations. However, these high-stakes decisions should be based on peer-reviewed and publicly available data and robust international scientific discussion.

The vaccines that are currently available are safe, effective, and save lives. The limited supply of these vaccines will save the most lives if made available to people who are at appreciable risk of serious disease and have not yet received any vaccine. Even if some gain can ultimately be obtained from boosting, it will not outweigh the benefits of providing initial protection to the unvaccinated. If vaccines are deployed where they would do the most good, they could hasten the end of the pandemic by inhibiting further evolution of variants. Indeed, WHO has called for a moratorium on boosting until the benefits of primary vaccination have been made available to more people around the world.18 This is a compelling issue, particularly as the currently available evidence does not show the need for widespread use of booster vaccination in populations that have received an effective primary vaccination regimen.