(7) Cellular and Humoral Responses to Vaccination Before or after SARS-CoV-2 Infection - Bridging the Knowledge Gap to End the Pandemic for Heart Transplant Recipients

PURPOSE: The degree of immunity provided by standard vaccine regimens, boosted regimens, and immune responses elicited by the combination of vaccination and natural infection remain unknown for the immunocompromised population. The relative magnitude, quality, and durability of serological responses, and the likelihood of neutralizing protection against future SARS-CoV-2 variants following these modes of exposure are unknown but are critical to the future trajectory of the COVID-19 pandemic. This study aims to directly compare the humoral and cellular immune responses among heart transplant recipients (HTxRs) who received COVID-19 vaccines before or after naturally acquired SARS-CoV-2 infection. METHODS: HTxRs were enrolled prospectively in the study belonging to three groups: vaccine-only (1-/2-/3-/4- doses vaccinated individuals with no history of COVID-19 or breakthrough infection), hybrid immunity (1-/2-/3-/4- doses vaccination after recovery from natural SARS-CoV-2 infection) and breakthrough infection (2-/3-/4- doses vaccinated individuals with PCR confirmed breakthrough infections). Vaccination protocol includes homologous primary/boosted BNT162b2 vaccine. Serum samples, collected longitudinally immediately before and 3 weeks after each dose or SARS-CoV-2 infection, were tested for SARS-CoV-2 anti-RBD IgG antibodies and for neutralizing antibodies (using live virus micro-neutralization assays) against wild-type sublineage B.1.1.50, the B.1.617.2 (delta) variant and four omicron variants (BA.1, BA.2, BA.4 and BA.5). SARS-CoV-2-specific-T-cell response were evaluated in a subset of patients by IFN-γ release of stimulated peripheral blood mononuclear cells. ENDPOINTS: 1) Neutralizing antibody titers against wild-type virus and the variants of concern after breakthrough infection, hybrid immunity, and vaccination alone; 2) T-cell response after breakthrough infection, hybrid immunity, and vaccination alone; and 3) Quality of the neutralizing antibody response