Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

ABSTRACT SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have documented serial Omicron infections. We characterized SARS-CoV-2 humoral responses in a healthy young person who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to those of 124 COVID-19 naive vaccinees. One month after the second and third vaccine doses, the participant’s wild-type and BA.1-specific IgG, ACE2 competition and virus neutralization activities were average for a COVID-19 naive triple-vaccinated individual. BA.1 infection boosted the participant’s responses to the cohort ≥95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Moreover, reinfection increased BA.1 and BA.2-specific responses only modestly. Results illustrate the risk of Omicron infection in fully vaccinated individuals and highlight the importance of personal and public health measures as vaccine-induced immune responses wane.