Omicron infection-associated T- and B-cell immunity in antigen-naive and triple-COVID-19-vaccinated individuals

Abstract

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2–3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.

Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections

“…Our study has strengths and limitations. First, we present detailed, in-depth immunological profiles of patients hospitalized with severe COVID-19 at admission, providing valuable insights into the immune responses of vaccinated and non-vaccinated individuals otherwise underreported in the literature ( 50 , 51 ). In contrast to other reports ( 48 , 49 ), we did not only focus on specific immune cells but had a rather broad approach with data on cytokine profiles, B cells, T cells, and T cell receptor profiles, activation, and exhaustion.…”

The Effect of Exposure to SARS-CoV-2 Vaccination and Infection on Humoral and Cellular Immunity in a Cohort of Patients with Immune-Mediated Diseases: A Pilot Study

“…Following omicron breakthrough infection, there is a durable reprogramming of neutralizing antibody responses, with a robust boosting of neutralization activity and an expansion of breadth against other omicron strains [ 23 ]. In HCWs, the responses to breakthrough omicron infection occurring after three doses are mainly due to cross-reacting B cells initially induced by vaccination, which generate B-cells that bind both the omicron and Wuhan spike proteins [ 24 ]. SARS-CoV-2 vaccines also elicit highly cross-reactive cellular immunity against the omicron variant, providing considerable protection against severe disease [ 25 ].…”

Comparative Analysis of Immune-response in Humans Infected by Alpha, Delta and Omicron Strains of SARS-CoV-2

“…Omicron is a variant of B cell immunity escape [Barros-Martins et al, 2023]. However, some roles of B cells are yet to be exposed, which are capable of obstructing the contagion.…”