Primer on what we know about mixing and matching Covid vaccines

TheAfter this week, a panel of experts advising the Centers for Disease Control and Prevention will hear about the results of a clinical trial that could affect how Covid vaccines are used in this country at some point in the future. The trial, conducted by the National Institute of Allergy and Infectious Diseases, is the so-called mix-and-match trial, to test Covid vaccines authorized in the United States in groups with each other.

The aim of the trial was to see if using a different vaccine as a booster injection improves protection. Does getting a dose of the Pfizer vaccine after getting one dose of Johnson & Johnson produce more antibodies than a second dose of J&J? Are the mRNA vaccines made by Pfizer and Moderna interchangeable, or does switching even there produce a wider range of immune responses?

This is not my opinion. The booster shot that most Americans are vaccinated with in the process of acquiring or holding it may not be the last required. A number of experts told STAT that knowing how to improve the use of the current generation of Covid vaccines is critical.


We need to recognize that many questions remain to be answered about the use of these vaccines, said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. We do not know the optimal dose. We do not know the most effective time period between doses. We don’t know how many doses we’ll need and we don’t know if we’ll have lasting protection if we mix the vaccines that each person receives.

In terms of how to use Covid vaccines, we are in the early days, Osterholm said, adding that now that we have effective vaccines, we need to start figuring out how best to use them. “We have to start adopting a public health mindset for decision making,” he said.


What follows is a primer on what we know about mixing COVID-19 vaccines.

Let’s start with the terms

If you get a booster injection of the same brand as your previous muffin or muffin, you get symmetric supporter. In the United States, most vaccinated people had identical series of vaccines and identical boosters.

There may be some exceptions. Earlier in the vaccine launch, when supplies were scarce, the CDC advised people that they could get a second injection of any available vaccine if they were due to get a second shot of the vaccine and there was no supply of the brand that was due. to have them. Available.

If your original series of vaccines or booster vaccines were from different manufacturers, you have what is called Heterogeneous Vaccine series or heterogeneous batch.

Few vaccines are designed to have heterogeneous booster benefits. For example, Johnson & Johnson’s Ebola vaccine uses two different types of vaccines — one made using a similar design to the company’s Covid vaccine. Similarly, the Sputnik V vaccine consists of two doses of similar but not identical vaccines, each made using a different adenovirus that has been modified to transfer genetic material from SARS-CoV-2 virus. In both cases, the goal was to ensure that the immune response to the first dose did not prevent the second shot from having an effect.

Necessity is the mother of invention

As mentioned above, most immunized people in the United States have been vaccinated with an identical series of vaccines. But heterogeneous systems have been used elsewhere for several different reasons.

In the early days of the vaccine’s release, some countries chose to use heterogeneous boosters because they did not have enough supplies to be able to give people a matching dose when it was time for their second dose. After the AstraZeneca vaccine was noted to cause serious clotting problems in some people who received it (a problem seen later with the J&J vaccine as well), some countries have discontinued its use or restricted its use to older adults, who are at risk of blood clots. The event after vaccination appears to be lower. Younger adults were offered one of the mRNA vaccines as a second dose instead.

Catherine Edwards, a vaccine researcher at Vanderbilt University, has suggested that the United States should likely consider whether to target specific brands of booster doses at certain populations — or, more specifically, if certain people should be turned away from certain vaccines. When the time comes for it. them to get reinforcement. With concerns about myocarditis in young males associated with mRNA vaccines and clotting problems reported mainly with younger women who have had one of the viral vaccines, such as J&J, it may be time to think about who gets which type of Covid vaccine, Edwards said.

A natural experience that turns into a border barrier

Countries such as the United Kingdom, Canada, France and Germany that have used heterogeneous vaccine approaches have created a travel dilemma for their citizens.

A number of countries – including the United States – do not consider people who have received two different types of vaccines to have been fully vaccinated, even if the person’s country of origin does. This means that a person who received the mRNA vaccine as a second dose after receiving an AstraZeneca injection as a first dose is not considered fully immunized and is ineligible to travel to the United States or other countries with the same rule.

Canada has approximately 4 million people who have been vaccinated according to a heterogeneous schedule. The United States and its northern neighbor share the world’s longest border, and in pre-Covid times, travel across it was active. Now many Canadians are in limbo, unsure if or when they will be allowed to cross into the US

Figuring out how to handle a range of vaccines used in a variety of ways around the world will be a challenge that the Biden administration and other governments will have to contend with as international travel increases.

Not all groups may be created equal

Could any combination of vaccine types or brands work as well — or better — than if all vaccines were from one brand? This is not yet clear, but it is possible – indeed likely – that the combinations and the order in which the vaccines are given matter.

“A followed by B may not be the same as B followed by A,” explained Bruce Gillen, head of global public health strategy for the Rockefeller Foundation’s Institute for Epidemic Prevention.

A number of small studies conducted in Europe have shown that follow-up of an AstraZeneca directed adenovirus vaccine with Pfizer or a modern The mRNA enhancer elicits a greater immune response than we would observe with two doses of AstraZeneca alone. But ongoing research efforts at Britain’s Oxford University to compare Covid vaccine formulations called Com-CoV trials suggest that the opposite may not be true.

Scientists conduct the original Com-CoV . experience Volunteers were given two doses each of AstraZeneca or Pfizer, to compare antibody levels with those obtained from the AstraZeneca followed by Pfizer or Pfizer followed by AstraZeneca regimens. After AstraZeneca, Pfizer produced higher antibody levels than two doses of AstraZeneca alone; But AstraZeneca after Pfizer was no better than two doses of Pfizer.

“The introductory event is really important,” he said. Barney Graham, who was deputy director of the National Institutes of Health’s Center for Vaccine Research until the end of August and who played an important role in the design of prototypes and Moderna vaccines.

Graham explained that the type of immune response one gets from Covid vaccines is determined by the first dose. “And so it kind of locks you in a repertoire and pattern of antibodies, T-cell balances that persist through subsequent reinforcements,” he said.

Graham said there is still much to learn about how to effectively mix Covid vaccines – and it will take time to answer those questions. “These are the things that happen during a 12-year development program. We didn’t do it this time.”

Mixed Punch Vaccines

In general, Covid vaccines are what is known as reactive; They can hold the wall. Fever, sore arms, tiredness, malaise – many people reported feeling kind of crazy within hours or even a day or two after getting their Covid shot.

Complaints about interactions were greater among people who received brands of mixed vaccines, and Com-CoV . experience mentioned. Therefore, it is likely that there will be more side effects after vaccination, but nothing that cannot be controlled. “It is reassuring that all the symptoms of the reaction were short-lived,” Com-CoV researchers said in a short study published in late May in The Lancet.

Next challenge

If evidence continues to accumulate that mixing brands of vaccines will be beneficial, how can this data be translated into public policy? Experts warn that it won’t be easy.

Regulators such as the Food and Drug Administration usually act on companies’ requests. They review the data provided by the manufacturer and decide yes, this vaccine or medicine can be given to these people or no, it should not be.

But when you talk about a plan that involves merging products from two different companies, things get more complicated. None of these companies has requested the use of a competitor vaccine used as a Covid vaccine booster – and they are unlikely to do so.

“Usually a manufacturer will put in a request to do something,” said Glenn Novak, director of the Center for Health and Risk Communication at the Grady College of Journalism and Mass Communication. “Who then has this responsibility to make a recommendation to mix and match? I think it’s a very good question.”

Norman Baylor, president and CEO of Biologics Consulting and former head of the FDA’s Office of Vaccines, said the CDC could address this problem. The advisory committee, ACIP, can evaluate the data and, if it supports the use of heterogeneous boosters, recommend that this is how the vaccines can be used. This advice can take the form of what is known as preferential recommendations – not actually saying that vaccine B should be used after vaccine A, but noting that it is advisable to do so.

Could that happen? Maybe. But if it does, it could potentially affect the way Covid vaccines are used in the future — in people who have not yet started vaccinating, or if people in the country need a fourth dose of the Covid vaccine. Because by the time there is enough data to move forward with this kind of policy, most Americans who deserve a booster shot will likely have had it.

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