Mix-and-match COVID boosters are as good—if not better than—all the same shots

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Mixing and matching COVID-19 vaccines for booster doses appears to be safer and more effective — if not more effective — than sticking with the same vaccine for booster doses. according to this Preliminary data posted online From a clinical trial run by the National Institutes of Health on Wednesday.

The trial gave something people had long hoped: that mix-and-match vaccines could provide strong, comprehensive protection against the pandemic virus and all its forms.

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The trial was not large enough to pinpoint with certainty which combination of vaccines provided the best protection. And the preliminary results available on a preprint server have not yet been peer-reviewed. But preliminary trial findings indicate that Moderna’s mRNA vaccine may provide the strongest protection around—supporting similar findings. East vaccine efficacy studies. The data also suggests that people who have received the one-shot Johnson & Johnson vaccine are more likely to receive a boost with one of two mRNA vaccines, either Moderna or Pfizer/BioNtech.

But most clearly, the study found that mix-and-match boosting increases protection and produces the same side effects as boosting with the same vaccine. Or, in the words of the authors: “These data suggest that if a vaccine is approved or authorized as a booster, an immune response will occur regardless of the primary COVID-19 vaccination regimen.”

nine combinations

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For the study, researchers from different testing sites across the country recruited 458 people over the age of 18. Afterwards the subjects were divided into three groups of about 150 each. Those three groups had different initial vaccine regimens: either two doses of Moderna Vaccine, two doses of Pfizer/BioNTech vaccine, or one shot of Johnson & Johnson vaccine.

From there, three groups of 150 each were divided into three groups of 50, with each of the smaller groups receiving different boosters. So, for example, out of 151 people who initially received the Moderna vaccine, 51 received the Moderna booster, 51 got the Pfizer/BioNtech booster, and 49 got the Johnson & Johnson booster. A booster dose was given between 12 and 29 weeks after the initial vaccination.

Next, the researchers looked at the levels of binding and neutralizing antibodies (so the boosters were able to kick in) on the day of the booster shot. The researchers checked the same levels 15 days later and 29 days later. In all combinations, the levels of binding antibodies increased between four-fold and 56-fold.

They also looked closely at neutralizing antibodies—antibodies that bind to and inhibit the SARS-CoV-2 virus from infected cells. In those who received the same type of vaccine for their initial dose and their booster dose, the level of neutralizing-antibody increased fourfold to twenty-fold. In those who received the different vaccines, the level of neutralizing-antibody increased six-fold to 76-fold.

The fold-change strongly indicated that the booster dose increased protection across the board, while mix-and-match may lead to an increase. But fold-changes can obscure some of the finer points. (You can see the full table of results Here, starting on page 27)

Looking at only average antibody levels in each group, subjects who initially received the Johnson & Johnson vaccine started on the first day with some of the lowest neutralizing-antibody levels. Their geometric mean titers of neutralizing antibodies ranged from 7.6 to 9 on the first day. As such, they had the smallest and largest fold-change after Boost. Members of the Johnson & Johnson group who received the Johnson & Johnson booster saw their neutralizing-antibody levels increase only fourfold after 15 days (up to 31) — the smallest change among all the groups. But those who got the Johnson & Johnson vaccine followed by Moderna Booster saw a 76-fold increase (up to 676) — the biggest change.

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Overall, those who received Moderna Booster had the highest neutralizing-antibody levels, regardless of which vaccine they had initially received. Their geometric mean titers of neutralizing antibodies ranged from 676 to 900 at day 15. The group with a median of 900—the highest level reported in the study—received Moderna Vaccine for its initial and booster doses. Those who initially received the Pfizer/BioNTech vaccine saw their geometric mean titers of neutralizing antibodies increase from approximately 25 to 786 after the modern booster.

People initially vaccinated with Moderna had better starting levels of neutralizing antibodies than those initially vaccinated with the Pfizer/BioNTech vaccine. Their range was 58-89 and 19-25 respectively. People initially vaccinated with the Pfizer/BioNTech vaccine and increased, their levels increased from 21 to 448. But it was still lower than those initially vaccinated with Moderna and boosted with Pfizer/BioNTech—they saw levels ranging from 58 to 678 after 25 days.

The researchers note that previous studies have estimated that a geometric mean titer of neutralizing antibodies at 100 or higher is related to a vaccine efficacy of 90.7 percent against symptomatic disease. All groups met that threshold, except for the group that received both the primary dose and booster dose of Johnson & Johnson.

Overall, the study indicates that mixing and matching is a safe and effective way to increase protection. Researchers will need to conduct larger studies to see if Moderna can maintain the lead it seems to be here. But when Food and Drug Administration advisers meet later this week to consider authorizing a Johnson & Johnson booster dose, Johnson & Johnson’s weak results will provide plenty of fodder for debate.

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