Superior neutralizing response after first versus second SARS‐CoV‐2 infection in fully vaccinated individuals

Abstract

Currently, the majority of the population has been vaccinated against COVID‐19and/or has experienced SARS‐CoV‐2 infection either before or after vaccination.The immunological response to repeated episodes of infections is not completelyclear. We measured SARS‐CoV‐2 specific neutralization titers by a pseudovirusassay after BA.1 infection and RBD‐specific immunoglobulin G (IgG), immuno-globulin A (IgA), and immunoglobulin M (IgM) in a cohort of COVID‐19uninfected and triple vaccinated individuals (breakthrough infection group,BTI) as compared with those previously infected by SARS‐CoV‐2 (reinfectiongroup, REI) who underwent identical vaccination schedule. SARS‐CoV‐2specificneutralizing response after BA.1 infection was significantly higher in the BTIgroup as compared with the REI. Furthermore, neutralization titers in REI werenot significant different from convalescent non reinfected controls. RBD‐specific IgG and IgA, but not IgM, werealso significantly higher in BTI ascompared with REI. Our results show that the first episode of SARS‐CoV‐2infection induces a significant increase inneutralizing titers in triple vaccinatedindividuals and that previous SARS‐CoV‐2 infection compromise significantly theneutralization response induced by reinfection, even by divergent SARS‐CoV‐2variants and at least up to 2 years postinfection, suggesting a fundamentallimitation in inducing effective booster through the intranasal route in previouslyinfected individuals