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

Abstract

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.

Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

“…In this cohort we also observed a negative association of age with induction of B cell memory. Although others have reported a negative association between age and serum antibody titers after a single mRNA vaccine dose 16,17 , we found that this relationship was not significant following two doses of mRNA vaccination. However, we observed that the magnitude of the memory B cell response following the second dose was lower with increased age, confirming age as a key variable in mRNA vaccine induced immunity.…”

“…Overall, these data also add to our understanding of SARS-CoV2 mRNA vaccine-induced immune responses in several ways. First, our serological data is consistent with several other recent studies 9,10,12,13,16,17 indicating robust boosting of antibody responses in SARS-CoV2 recovered subjects after the first vaccine dose, but little benefit to antibody titers after the second vaccine dose. Moreover, we identified a similar effect for virus-specific memory B cells, demonstrating that both a quantitative and qualitative plateau in vaccine-induced memory B cells is achieved following the first dose of vaccine with little additional change to the memory B cell response following booster vaccination.…”

“…Several previous studies have reported a negative association between age and vaccine-induced antibody titers after a single dose of mRNA vaccines 16,17 . We therefore investigated potential relationships between sex or age and B cell responses after one or two doses of vaccine.…”

Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination

“…A subset of recovered individuals (70%) did appear to have increased AIM + CD8 + T cell frequencies compared with baseline, but as a group this increase did not reach statistical significance (Figure S1E). In contrast to the modestly weaker induction of antibodies and memory B cells with increasing age observed in this cohort and others (Abu Jabal et al, 2021;Goel et al, 2021;Levi et al, 2021;Prendecki et al, 2021), T cell responses upon mRNA vaccination were not correlated with age (Figure S1F). Taken together, these data demonstrate robust induction of antigen-specific T cell responses following mRNA vaccination, with more consistent induction of CD4 + T cell responses compared with CD8 + T cell responses.…”

One dose of SARS-CoV-2 vaccine exponentially increases antibodies in individuals who have recovered from symptomatic COVID-19

“…However, there is no indication as to whether individuals previously exposed to SARS-CoV-2 should be vaccinated or how many times they should receive a vaccine. We and others have shown that antibody response increases robustly after the first dose in SARS-CoV-2-exposed individuals (6)(7)(8)(9). By contrast, a second dose of vaccine does not seem to further increase the antibody response and may even have a detrimental effect on antigen-specific immune responses (10).…”