Prior SARS-CoV2 infection in vaccinated solid organ transplant recipients induces potent neutralization responses against variants, including Omicron (preprint)

Factors affecting functional antibody responses in solid organ transplant recipients (SOTRs) to current SARS-CoV2 vaccines are not well understood. Here, we measured vaccine-induced neutralizing activities against the D614G-CoV2 baseline virus and eight variants, including Omicron, in a panel of CoV2 infected- (n=13) and uninfected- (n=63) vaccinated kidney and heart transplant recipients. In the CoV2 uninfected-vaccinated subset, only 19% and 35% of two and three-dose vaccinated recipients respectively possessed minimally protective neutralizing plasma antibody titers (IC50>1:50) against D614G. In contrast, all of the CoV2 infected-vaccinated SOTRs who received two vaccine doses possessed titers exceeding minimal protection; 12/13 exhibiting strong protection (IC50>1:600) against D614G with minimal increases provided by a third dose. Omicron was the most resistant variant: only 10% of CoV2 uninfected-vaccinated SOTRs reached the minimally protective neutralization titer, while 76% of CoV2 infected-vaccinated SOTRs exceeded this value. These results indicate that prior infection and vaccination can induce highly protective antibody responses in many SOTRs, and identify important factors (shorter time since transplantation, prednisone administration, and African American ethnicity) that limit these responses. Overall, these results suggest factors to consider in establishing optimum COVID-19 vaccination strategies in these cohorts.

Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells (preprint)

Given the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the recent implementation of SARS-CoV-2 vaccination, we have much to learn about the duration of immune protection and the interface between the immune responses to infection and to vaccination. To address these questions, we monitored immune responses to SARS-CoV-2 infection in convalescent individuals over seven months and following mRNA vaccination. Spike Receptor-Binding-Domain (RBD)-specific circulating antibodies and plasma neutralizing activity generally decreased over time, whereas RBD-specific memory B cells persisted. Additionally, using antibody depletion techniques, we showed that the neutralizing activity of plasma specifically resides in the anti-RBD antibodies. More vigorous antibody and B cell responses to vaccination were observed in previously infected subjects relative to uninfected comparators, presumably due to immune priming by infection. SARS-CoV-2 infection also led to increased numbers of double negative B memory cells, which are described as a dysfunctional B cell subset. This effect was reversed by SARS-CoV-2 vaccination, providing a potential mechanistic explanation for the vaccination-induced reduction in symptoms in patients with "Long-COVID".