Third COVID-19 Vaccine Dose Boosts Neutralizing Antibodies in Poor Responders

Background: While evaluating COVID-19 vaccine responses using a rapid neutralizing antibody (NAb) test, we observed that 25% of mRNA vaccine recipients did not neutralize >50%. We termed this group "vaccine poor responders" (VPRs). The objective of this study was to determine if individuals who neutralized <50% would remain VPRs, or if a third dose would elicit high levels of NAbs.

Methods: 269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccines were evaluated. NAb levels were measured: (i) 2-4 weeks after a second vaccine dose, (ii) 2-4 months after the second dose, (iii) within 1-2 weeks prior to a third dose and (iv) 2-4 weeks after a third mRNA vaccine dose.

Results: Analysis of vaccine recipients reveals that 25% did not neutralize above 50% (Median neutralization = 21%, titers <1:80) within a month after their second dose. Twenty-three of these VPRs obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, VPRs show an average 5.4-fold increase in NAb levels (range: 46-99%).

Conclusions: The results suggest that VPRs are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose. Although it is not known what levels of NAbs protect from infection or disease, those in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, and potential transmission.