COVID-19 Antibodies After 1 and 2 Pfizer Vaccine Boosters

COVID-19 mRNA vaccines, though still effective against severe or fatal disease, are known to wane over time. This is exacerbated by the emergence of new, highly infectious variants, such as Delta and Omicron.

In Israel, a fourth Pfizer-BioNTech shot was approved for persons 60 years and older after the efficacy of 3 Pfizer-BioNTech vaccinations (a 2-dose primary series and 1 booster shot) was deemed insufficient against Omicron.

A JAMA study published today compared the immune response to a third and fourth Pfizer-BioNTech (BNT162b2) vaccine. The investigators evaluated the antispike (anti-S) immunoglobin G (IgG) antibody titers before and after each dose.

The cohort included 99 participants aged 60 years and older who received at least 3 doses of Pfizer-BioNTech; the average age was 70 years and the cohort was 61% female. Of the 99, 57 received an additional fourth dose. The population was considered at high risk of developing severe COVID-19 disease, and represented those first eligible for third and fourth Pfizer-BioNTech vaccine doses.

The investigators assessed the cohort’s anti-S IgG titers before and 10-19 days after their third Pfizer-BioNTech dose, as well as before and 8-17 days after their fourth dose. Before the fourth dose, all participants were seropositive.

Average IgG titers significantly increased after the third dose (450 AU/mL before dose 3 and 27092 ~14 days after the dose) and after the fourth dose (3775 AU/mL before dose 4 and 28708 AU/mL ~11 days after the dose). There was no significant correlation between age and IgG titer after dose 4.

Of the 57 participants who received 4 vaccine doses, 7% contracted COVID-19 (n = 4). Among those who received only 1 booster, 21% contracted COVID-19 (n = 9). All infections were asymptomatic to mild. There were no major adverse events reported.

This study found that in adults 60 years and older, a third and fourth dose of the Pfizer-BioNTech COVID-19 vaccine safely and significantly increased anti-S IgG titers approximately 2 weeks after vaccination. The investigators noted that they did not examine the waning of immune response after the fourth dose, and thus further study should be done to determine whether subsequent boosters are required.