Conclusions
Parenterally administered COVID-19 vaccines do not generate sufficient mucosal-type IgA responses despite strong systemic IgG responses to SARS-CoV-2. These results demonstrate the necessity and importance of reevaluating vaccine design and scheduling to efficiently increase oral or respiratory mucosal immunity against SARS-CoV-2.
Methods
We examined the longitudinal kinetics of SARS-CoV-2 spike RBD-specific IgA and IgG responses in sera of Japanese healthcare workers (HCWs) after receiving two doses and the third dose of BNT162b2 mRNA vaccines. During the prospective cohort study, Omicron breakthrough infections occurred in 62 participants among 370 HCWs who had received triple doses of the vaccine. Pre-breakthrough sera of infected HCWs and non-infected HCWs were examined for the levels of anti-RBD IgA and IgG titers.
Results
The seropositivity of anti-RBD IgA at 1 M after the second vaccine (2D-1M) and after the third dose (3D-1M) was 65.4% and 87.4%, respectively, and wanes quickly. The boosting effect on anti-RBD Ab titers following breakthrough infections was more notable for anti-RBD IgA than for IgG. There were partial cause-relationships between the lower anti-RBD IgA or IgG at pre-breakthrough sera and the breakthrough infection. Conclusions: Parenterally administered COVID-19 vaccines do not generate sufficient mucosal-type IgA responses despite strong systemic IgG responses to SARS-CoV-2. These results demonstrate the necessity and importance of reevaluating vaccine design and scheduling to efficiently increase oral or respiratory mucosal immunity against SARS-CoV-2.