SARS-CoV-2 humoral and cellular immunity following different combinations of vaccination and breakthrough infection

Abstract

The elicited anti-SARS-CoV-2 immunity is becoming increasingly complex with individuals receiving a different number of vaccine doses paired with or without recovery from breakthrough infections with different variants. Here we analyze the immunity of individuals that initially received two doses of mRNA vaccine and either received a booster vaccination, recovered from a breakthrough infection, or both. Our data suggest that two vaccine doses and delta breakthrough infection or three vaccine doses and optionally omicron or delta infection provide better B cell immunity than the initial two doses of mRNA vaccine with or without alpha breakthrough infection. A particularly potent B cell response against the currently circulating omicron variant (B. 1.1.529) was observed for thrice vaccinated individuals with omicron breakthrough infection; a 46-fold increase in plasma neutralization compared to two vaccine doses (p < 0.0001). The T cell response after two vaccine doses is not significantly influenced by additional antigen exposures. Of note, individuals with hybrid immunity show better correlated adaptive immune responses compared to those only vaccinated. Taken together, our data provide a detailed insight into SARS-CoV-2 immunity following different antigen exposure scenarios.

Humoral and cellular immune responses in fully vaccinated individuals with or without SARS‐CoV‐2 breakthrough infection: Results from the CoV‐ADAPT cohort

“…Our data suggest a shift from a vaccination‐induced, balanced immune response towards a quantitative predominance of the humoral component following breakthrough infections, apparent in significantly increased antibody levels accompanying unaltered TC in subjects with compared to subjects without breakthrough infection. This finding is supported by a previous study demonstrating that T‐cell responses are not significantly altered by additional antigen exposure through breakthrough infection after two SARS‐CoV‐2 vaccinations; however, in line with our observations a third vaccination was capable to increase the T‐cell response 32 . The lack of breakthrough‐induced T‐cell stimulation may be attributable to the previously reported T‐cell exhaustion following natural SARS‐CoV‐2 infection 33–35 .…”

Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy

“…In the general population, the combination of vaccine and infection boosts antibody responses compared to either immune exposure alone (56,85,109,110). This similarly occurs in pregnancy where levels of antibody functions, Fc receptor binding and subclasses with the combination is statistically significantly higher compared to infection alone and non-significantly higher compared to vaccine alone (Figure 1, 2).…”

“…Diversity of the Fc domain through differential subclass and post-translational glycosylation modulates binding to Fc receptors and the spectrum of effector functions (45)(46)(47)(48)(49)(50)(51)(52). Moreover, antibody functional potency, breadth and coordination between neutralizing and Fc effector responses likely contribute to protection (26,(53)(54)(55)(56)(57). Some data demonstrate that maternal immune adaptation to pregnancy alters antibody subclass and glycosylation (30,(58)(59)(60)(61)(62)(63)(64)(65), but the implications for antibody functions and what exists for the fetus are only just beginning to be appreciated (66)(67)(68)(69)(70).…”

Behandlungsansätze für das Post-Covid-Syndrom

“…Es gibt zahlreiche pathogenetische Erklärungsversuche. Die SARS-CoV-2-Infektion führt oft zu einer starken und länger anhaltenden Immunaktivierung, auch nach vorheriger Impfung 7 . Von Bedeutung ist eine anhaltende Entzündungsreaktion mit im Vergleich zu Genesenen erhöhten Spiegeln von Zytokinen und Interferonen sowie aktivierten T-Zellen 8 9 .…”

“…PCS-ähnliche Zustände gibt es nicht zuletzt nach Impfungen gegen SARS-CoV-2. Sie werden als Post-Vakzine-Syndrom, Post-Vac-Syndrome oder Post-Vakzinierungssyndrom (PVS) bezeichnet 14 15 16 .…”