Vaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin

Abstract

Several studies have suggested the imprinting of SARS-CoV-2 immunity by original immune challenge without addressing the formation of the de novo response to successive antigen exposures. As this is crucial for the development of the original antigenic sin, we assessed the immune response against the mutated epitopes of omicron SARS-CoV-2 after vaccine breakthrough. Our data demonstrate a robust humoral response in thrice-vaccinated individuals following omicron breakthrough which is a recall of vaccine-induced memory. The humoral and memory B cell responses against the altered regions of the omicron surface proteins are impaired. The T cell responses to mutated epitopes of the omicron spike protein are present due to the high cross-reactivity of vaccine-induced T cells rather than the formation of a de novo response. Our findings, therefore, underpin the speculation that the imprinting of SARS-CoV-2 immunity by vaccination may lead to the development of original antigenic sin if future variants overcome the vaccine-induced immunity.

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“…Pušnik et al observed that, while T-cell responses to omicron's mutated epitopes persisted due to vaccine-induced cross-reactivity, humoral and memory B-cell responses against the altered regions were weakened. This implies that prior vaccination could potentially predispose individuals to OAS if future variants evade vaccine-induced immunity [241]. This is indeed a consideration for the development of second-generation COVID-19 vaccines, where the vaccines are effective against emerging variants of SARS-CoV-2.…”