Impact of SARS-CoV-2 infection on longitudinal vaccine immune responses

Background Recent serological investigations imply waning immune responses following SARS-CoV-2 vaccination, but prior infection may impact the breadth and duration of vaccine immune responses. Methods Using longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU/ml) and neutralizing antibody titers against ten SARS-CoV-2 variants over seven months following BNT162b2 in healthcare workers with (n=111) and without (n=298) confirmed prior SARS-CoV-2 infection. A smaller group with (n=47) and without (n=61) confirmed prior SARS-CoV-2 infection receiving ChAdOx1 ncov-19 was followed for three months. Results Vaccination (BNT162b2 and ChAdOx1 ncov-19) following SARS-CoV-2 infection resulted in higher wild-type BAU/ml geometric mean titers (GMTs) at all sampling time points when compared to SARS-CoV-2 naive vaccinees (all p<0.001). GMTs were 1875 BAU/ml in convalescent and 981 BAU/ml in naive BNT162b2 vaccinees 6 weeks post vaccination. 29 weeks post vaccination, GMTs had decreased to 524 BAU/ml in convalescent and 148 BAU/ml in naive vaccinees. GMT differences between convalescents and naive following ChAdOx1 ncov-19 mirrored those after BNT162b2, but the titers were considerably lower. Finally, at all time points, neutralizing antibody titers against all ten tested SARS-CoV-2 variants were at least 2 respectively 3-fold higher in SARS-CoV-2 recovered as compared to naive vaccinees following BNT162b2 and ChAdOx1 ncov-19, respectively (all p<0.001). Conclusions These findings of substantially more robust serological responses to vaccine after natural infection imply that prior infection may be taken into consideration when planning booster doses and design of current and future SARS-CoV-2 vaccine programs.