Experts debate vaccine dose manipulation as virus spirals out of control

As the pandemic continues to climb to new heights, a debate has erupted among experts on how to get the most protection as quickly as possible in the face of the limited supply of COVID-19 vaccines currently available.

Suggestions offered so far include postponing the second two-dose regimen for perhaps three to four months rather than dispensing them in the planned three to four week intervals evaluated in large clinical trials. With this change, more people can receive a first dose now, offeringsome protection. Another possibility is to simply halve the doses, which would immediately double the number of people who can be vaccinated now. And regulators in the UK have introduced the idea of ​​mixing treatment regimens – with some people receiving their first dose of a vaccine from one manufacturer, then receiving a second dose of vaccine from another manufacturer depending on the availability of the vaccine. moment.

The evidence to support these suggested changes in vaccine deployment is tenuous at best. But some experts say the dire state of the pandemic warrants a new, possibly riskier approach.

Viral strike

“[A]s Mike Tyson said, “Everyone has a plan until they get punched in the mouth,” Robert Wachter, director of the Department of Medicine at the University of California at San Francisco, and Ashish Jha, dean of Brown University’s School of Public Health, wrote in an op-ed in the Washington Post on Sunday. In the opinion piece, the pair make an argument for delaying second doses, writing: “When it comes to COVID-19, we get punched in the mouth over and over again. It’s time to change plans. “

Wachter and Jha note that the researchers did not examine what happens if a person takes only one dose of a two-dose vaccine schedule. In the United States, the Food and Drug Administration has cleared the use of Moderna’s COVID-19 mRNA vaccine and another mRNA vaccine made by Pfizer and BioNTech. In large Phase III clinical trials, both vaccines have shown about 95% effectiveness in protecting against COVID-19 – but only after two doses given at 28 days (Moderna) or 21 days (Pfizer / BioNTech) d ‘interval. It is not known how effective the vaccine is after a single dose and how long this protection might last.

The single-dose strategy “has not been studied, so we don’t know if and when first-time immunity starts to wane,” write Jha and Wachter. “But, they continue, the data from Moderna, for example, is reassuring. It shows a robust immune response four weeks after the first shot, and most experts find it extremely unlikely that immunity will drop somehow by week eight or even week 12 afterwards. a single shot.

Risks and unknowns

This thought seemed sufficient to influence health officials in the UK. Last week they announced that they would allow the interval between the first and second shot at 12 weeks. They also opened up the possibility that people could receive first and second doses of vaccine from different manufacturers – for example, a person could receive a first dose of Pfizer / BioNTech vaccine followed by a dose of a COVID-19 vaccine d ‘AstraZeneca / University of Oxford. (The AstraZeneca vaccine is another two-dose vaccine that was approved in the UK last week. US officials expect the FDA to grant it emergency clearance in the coming months.)

But other experts are still strongly opposed to delaying a second dose. Although immune responses do not “drop” dramatically in a few months, they will subside over time. And, since researchers do not yet know what level of immune responses are needed to prevent infections and disease, it cannot be said that a single dose will be enough to keep people from getting infected or sick.

In addition, the decrease in immune responses after a dose could possibly make the coronavirus more dangerous. Some experts have noted that the virus which circulates widely mixes with many people low immune responses could create the perfect selective pressure for the virus to adapt to escape those immune responses. Coronaviruses naturally mutate over time, and several variants – including those from the UK and South Africa – have already arisen and appear to spread more easily among people. So far, these variants do not appear to cause more serious or fatal illnesses. And they’re not thought to escape the immune responses of natural infections or licensed vaccines. But, partially vaccinating large numbers of people could lead to these nightmare scenarios, some experts fear.

Stick to science

Given the uncertainties and risks, many experts strongly oppose manipulation of the vaccination plan. This includes top infectious disease expert Anthony Fauci. Last Friday, Fauci lambasted the idea of ​​the US following the UK’s lead by allowing a delayed second dose. “I wouldn’t be in favor of that,” Fauci said in an interview with CNN.

“The point is, we want to stick with what the science tells us and what data we have for both. [vaccines] state that you are giving a bounty, followed by a boost in 21 days with Pfizer and 28 days with Moderna, ”Fauci said. “And now that’s how we’re going with it, and that’s the decision that’s been made.”

Moncef Slaoui, chief scientist of the US government’s Operation Warp Speed, echoed Fauci’s opposition to postponing second doses in an interview on CBS on Sunday ‘ Face the nation.

“We have always said that these vaccines will be developed on the basis of science and that all decisions will be made transparently on the basis of data,” Slaoui said. “Changing the decisions made, the choices made, which was to give two doses of vaccine – the second dose gives you an immune response ten times higher than the first dose – without any data I think would not be responsible.

However, oddly enough, Slaoui offered another alternative to maximize vaccine deployment:

“Here is the alternative. We know that for the Moderna vaccine, giving half the dose to people between the ages of eighteen and fifty-five – two doses, half the dose, which means exactly meeting the goal of vaccinating twice the number. of people with the doses that we have – we know that it induces an immune response identical to the dose of one hundred micrograms and therefore we are in discussion with Moderna and with the FDA.

“Of course, that will ultimately be a decision of the FDA,” Slaoui said. But, he added, “I think it’s a more responsible approach that will be based on facts and data.”