ABSTRACT
Background A cluster of over a thousand infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. Immune responses in breakthrough infections with the SARS-CoV-2 delta variant remain to be defined. Methods Humoral and cellular immune responses were assessed in 35 vaccinated individuals who were tested for SARS-CoV-2 in the Massachusetts Department of Public Health outbreak investigation. Results Vaccinated individuals who tested positive for SARS-CoV-2 demonstrated substantially higher antibody responses than vaccinated individuals who tested negative for SARS-CoV-2, including 28-fold higher binding antibody titers and 34-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed 4.4-fold higher Spike-specific CD8+ T cell responses against the SARS-CoV-2 delta variant than vaccinated individuals who tested negative. Conclusions Fully vaccinated individuals developed robust anamnestic antibody and T cell responses following infection with the SARS-CoV-2 delta variant. These data suggest important immunologic benefits of vaccination in the context of breakthrough infections.