Individuals 60 years and older who were originally vaccinated with two doses of Pfizer BioNTech COVID-19 vaccine were better protected against the Omicron variant coronavirus after being boosted with a Moderna vaccine rather than another dose of Pfizer’s BioNTech vaccine.
These results are corresponding based on preliminary data from a small but randomized controlled clinical trial in Singapore and published this week in the journal Clinical Infectious Diseases.
The study — which included 98 healthy adults — can’t determine whether the Moderna booster is simply superior to a Pfizer-BioNTech booster for older adults, or if a mix-and-match booster strategy is inherently better. It also focused solely on antibody levels, which may or may not result in significant differences in infection rates and other clinical differences. It also followed humans just 28 days after a booster, so it’s unclear if the Moderna booster benefit will last over time.
Still, the authors of the study, led by Barnaby Young of Singapore’s National Center for Infectious Diseases, report that the positive effect of switching from Pfizer-BioNTech to Moderna was so significant that they don’t expect it to go away with more participants . It also follows other studies that suggest mix-and-match boosting — also known as heterologous boosting — can generate slightly different antibodies and Reducing the incidence of SARS-CoV-2 infection in people over 60 years of age.
For the new study, Young and colleagues looked at antibody levels in adults of all ages who received two doses of Pfizer-BioNTech COVID-19 vaccine between six and nine months before receiving a booster dose. The researchers excluded people from the study if they had a compromised immune system or had evidence of previous SARS-CoV-2 infection (presence of anti-N antibodies).
Of the 98 participants, 50 received an additional dose of Pfizer-BioNTech vaccine for their booster dose (homologous booster), while the remaining 48 received a Moderna booster (heterologous booster). The authors looked at their resulting antibody responses on the day of their booster dose, seven days later, and 28 days later. Specifically, they compared total levels of antibodies targeting a key part of the SARS-CoV-2 spike protein called the receptor-binding domain. They also looked at the levels of neutralizing antibodies against a range of specific SARS-CoV-2 variants, from the ancestral strain to alpha, beta, delta and omicron.
Slightly more boost
Overall, the heterologously boosted group had slightly higher total antibody levels than the homologous group — about 40 percent higher at day seven and 30 percent higher at day 28, although the confidence intervals overlapped. But when the authors broke down the groups by age, they found that the benefit was based entirely on the differences in the over-60s group. Antibody levels were the same in younger participants regardless of the type of booster.
Among the over 60s were 24 homologously boosted participants and 23 heterologously boosted participants. Seven days after the booster dose, the heterologously boosted participants had two-fold higher antibody levels than the homologous group and 60 percent higher levels at 28 days.
Older heterologously boosted participants also had higher levels of neutralizing antibodies against all SARS-CoV-2 variants tested – with the biggest difference versus Omicron, which is known to thwart vaccine-derived immune responses. After seven days, the level of inhibition of neutralizing antibodies was 89 percent in the heterologously boosted group compared to 64 percent in the homologously boosted group. At 28 days, spread was 84 percent in the heterologously boosted group versus 73 percent in the homologously boosted group.
Overall, Young and co-authors concluded: “Particularly for the vulnerable older age group, a heterologous booster COVID-19 vaccine regimen induces a higher anti-spike antibody titer and a stronger neutralizing antibody response against the highly infectious Omicron variant (~20 percent higher neutralization) than a homologous refresher.”
The study is ongoing, so the authors will continue to add participants and data. They intend to re-evaluate antibody responses in all participants six months and 12 months after the booster dose. They will enroll people in the study who originally received Moderna vaccines to see if switching to the Pfizer-BioNTech vaccine for the booster dose provides a similar benefit.
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