Covid-19: Does research back up the US’s mix-and-match booster shot policy?

The US Food and Drug Administration (FDA) recently approved a mix-and-match booster shot plan that allows the eligible adult population to choose from one of three vaccines — Moderna, Pfizer-BioNTech, or Johnson & Johnson — even if it’s different from the first two doses.

The decision has led to confusion among people, who are caught in two minds between switching vaccines for the booster shot or sticking with the one they have already taken.

Public health officials in the US have left it to individuals to decide and refused to recommend a specific shot.

Mixing and matching of booster shots
One reason that US experts considered to approve the mix-and-match booster shot strategy is convenience. The authorities believe the strategy will help achieve its target of helping vulnerable people quickly get boosters.

But the expert panel was also following science. Early studies have found that mixing and matching vaccines is not only effective, but can also create a broader and more potent response than multiple doses of a single vaccine.

Why a specific booster shot isn’t recommended
While the scientific studies didn’t find a clear winner, it showed that all the booster shots provided strong antibody response, regardless of the combination.

University of Maryland School of Medicine Professor Dr. Kirsten E. Lyke told The New York Times that the mix-and-match solution enabled people no matter where they were to have a choice. Dr. Lyke, who presented the early results of the booster shot trial to the US FDA’s vaccine panel, said they were all safe, they would all give a boost, and they were all going to protect against severe disease and death.

What the studies show
The National Institutes of Health in June began a study to look at how people vaccinated with Moderna, Pfizer, or Johnson & Johnson reacted to a booster dose of the same shot or a new one. The researchers studied nine vaccine and booster combinations, with each group having 50 volunteers each.

Early results found that all the booster shots stimulated a neutralising antibody response. These are specific antibodies that stop the virus. But there were stark differences — those who had taken the Moderna vaccine for the first two doses and the Moderna booster had the highest antibody levels. People who got two doses of Pfizer, followed by a Moderna booster, had the second highest antibody count.

However, the small study groups were not designed to compare which shot was the best. The first studies used the full 100-microgram dose of the Moderna shot instead of the approved half dose. It is possible that differences in study subjects led to the difference in results. While the difference in antibody levels seems impressive, it probably cannot provide meaningful protection in the real world.

Johnson & Johnson recipients displayed the biggest differences, with a four-fold rise in neutralising antibodies after a booster of the same vaccine, but a 76-fold rise after the Moderna booster. The Pfizer booster led to a 35-fold increase.

Does that mean a Johnson & Johnson recipient should switch to Moderna or Pfizer?
Johnson & Johnson recipients, who initially would have received one dose, should consider another study that included 30,000 volunteers and looked at overall protection. This study found that a second Johnson & Johnson dose, at least two months after the first, offered 94% protection against mild-to-severe Covid-19.

The Johnson & Johnson vaccine, studies found, triggered a different part of the immune system. It stimulates not just neutralising antibodies but also T cells, thus resulting in protection that is more durable. The National Institutes of Health will eventually extend its study to consider T-cell response following various booster shot combinations. However, the data hasn’t been made public yet.

How to decide which booster to pick
All the booster shots stimulate immune response. So, choosing a booster shot depends on the priorities and personal risk.

Talk to a doctor: Depending on personal health circumstances, a physician might be able to choose the best opinion for an individual. Different vaccines can have different side effects on an individual.

Convenience: In terms of convenience, one can choose the shot that is easiest to get.

Concerns about risk: People anxious about Covid-19 can decide to base their decision about the booster shot on preliminary research and choose Moderna, which is found to stimulate higher neutralising antibodies.

Familiarity: Some people may choose on the basis of their previous experience. They are aware of how their body handled the first dose and may be inclined to pick the same dose for the booster.

Dr. Asaf Bitton of Harvard T.H. Chan School of Public Health said he received several questions from patients about the choice of shot. His advice for patients who received the Johnson & Johnson vaccine is to mix and match with the Pfizer or Moderna shot, based on data from the preliminary study. But for patients who have received the mRNA-based Moderna or Pfizer, he suggests sticking with the same shot.

Does Moderna’s dosage for the booster matter?
The National Institutes of Health study is looking at any likely difference in response between those who received the full 100-microgram dosage of the Moderna vaccine and those who received half a dose. While the results are not available yet, experts said it was unlikely that there would be much difference.

How long does the booster last?
While there is no answer to that question, scientists are studying large groups of people to arrive at a conclusive result.

Booster mania
Children’s Hospital of Philadelphia Vaccine Education Center Director Dr. Paul A. Offit said the question was to what extent the booster mania would affect the pandemic.

He said if the virus led to hospitalisation, it would not be because of missing a third dose but not getting any dose.