Recent SARS-CoV-2 infection abrogates antibody and B-cell responses to booster vaccination

Abstract

SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a two-month period, we evaluated antibody and B-cell responses to a third dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies, and memory B cells. Spike-specific B-cell responses from recent infection were elevated at pre-boost but comparatively less so at 60 days post-boost compared to uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B-cell responses to booster vaccines are impeded by recent infection.

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV

“…We measured frequencies of RBD-and NTD-specific B cells (RBD + S1 + and NTD + S1 + , respectively) among total B cells by spectral flow cytometry using a 19-color subset (Table S24) of a previously described 21-color panel (62). Briefly, the biotinylated spike proteins were tetramerized with fluorescently labeled streptavidin at a molar ratio of 4:1 as described previously (63), with minor modifications (62).…”

“…We measured frequencies of RBD-and NTD-specific B cells (RBD + S1 + and NTD + S1 + , respectively) among total B cells by spectral flow cytometry using a 19-color subset (Table S24) of a previously described 21-color panel (62). Briefly, the biotinylated spike proteins were tetramerized with fluorescently labeled streptavidin at a molar ratio of 4:1 as described previously (63), with minor modifications (62). Cryopreserved PBMCs were thawed and stained with Zombie NIR Fixable Viability Dye, followed by staining with a cocktail of mAbs and four fluorochromeconjugated spike proteins in staining buffer (2% FBS/PBS) supplemented with Brilliant Stain Buffer Plus (BD Biosciences).…”