Third SARS-CoV-2 vaccination and breakthrough infections enhance humoral and cellular immunity against variants of concern

Abstract

IntroductionSARS-CoV-2 vaccination is the leading strategy to prevent severe courses after SARS-CoV-2 infection. In our study, we analyzed humoral and cellular immune responses in detail to three consecutive homologous or heterologous SARS-CoV-2 vaccinations and breakthrough infections.MethodsPeripheral blood samples of n=20 individuals were analyzed in the time course of three SARS-CoV-2 vaccinations and/or breakthrough infection. S1-, RBD-, S2- and N-specific IgG antibodies were quantified using Luminex-based multiplex assays and electrochemiluminescence multiplex assays for surrogate neutralization in plasma. Changes in cellular immune components were determined via flow cytometry of whole blood samples.ResultsAll individuals (n=20) responded to vaccination with increasing S1-/RBD-/S2-specific IgG levels, whereas specific plasma IgA displayed individual variability. The third dose increased antibody inhibitory capacity (AIC) against immune-escape variants Beta and Omicron BA.1 independently of age. The mRNA-primed vaccination induced IgG and IgA immunity more efficiently, whereas vector-primed individuals displayed higher levels of memory T and B cells. Vaccinees showed SARS-CoV-2-specific T cell responses, which were further improved and specified after Omicron breakthrough infections in parallel to the appearance of new variant-specific antibodies.DiscussionIn conclusion, the third vaccination was essential to increase IgG levels, mandatory to boost AIC against immune-escape variants, and induced SARS-CoV-2-specific T cells. Breakthrough infection with Omicron generates additional spike specificities covering all known variants.

SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire

“…Increases in S-specific T cell responses have also been previously noted by others following mild or moderate BTI. 33 , 64 , 65 , 66 , 67 , 68 However, this increase was not observed in more severe and critical cases of infection where instead a delayed S-specific T cell response was observed. 69 Here, the largest increases in SARS2-specific T cell responses were observed in individuals with no pre-existing memory of non-S antigens.…”

A two-arm analysis of the immune response to heterologous boosting of inactivated SARS-CoV-2 vaccines

“…Memory T cell responses in 11 of 12 participants after heterologous DNA vaccination followed by boosting with mRNA vaccine were increased in both CD4+ and CD8+ T cells 33 . A study of memory T cell phenotypes after first vaccination showed increased numbers of EM and TEMRA CD4+ or CD8+ T cells but these were lower after the second and the third vaccination 34 . Our study is the first observation in a Thai heterologous booster vaccination program which investigates changes in memory T cell subpopulations upon in vitro stimulation of PBMC with Omicron peptide, compared to unstimulated circulating cells.…”

Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19

“…Furthermore, a reduced in vitro antibody inhibition capacity of non-hospitalized patients especially against delta and beta variants of SARS-CoV-2 was found, which might explain breakthrough infection of patients with mild course of disease. The importance of repetitive vaccinations has been shown by Ruhl et al [ 22 ]. In the multivariate analysis, CD4 + T cell counts were positively correlated with post-acute FAS score.…”