A cautionary note on recall vaccination in ex-COVID-19 subjects

Levi, R.; Azzolini, E.; Pozzi, C.; Ubaldi, L.; Lagioia, M.; Mantovani, A.; Rescigno, M.

Currently approved COVID-19 vaccines based on mRNA or adenovirus require a first jab followed by recall immunization. There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses. Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID). Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naive subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine. We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR. Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects. On the contrary, a second dose might switch-off the immune response due to antigen exhaustion, which occurs in response to several viruses or drive the development of low-affinity antibodies for SARS-CoV-2 which may foster an antibody dependent enhancement (ADE) reaction when re-exposed to the virus. These results question whether a second shot in ExCOVID subjects is indeed required and suggest to post-pone it while monitoring antibody response longevity.