Long-term COVID-19 vaccine- and Omicron infection-induced humoral and cell-mediated immunity.

Introduction: Mutations occurring in the spike (S) protein of SARS-CoV-2 enables the virus to evade COVID-19 vaccine- and infection-induced immunity.
Methods: Here we provide a comprehensive analysis of humoral and cell-mediated immunity in 111 healthcare workers who received three or four vaccine doses and were followed up to 12 and 6 months, respectively, after the last vaccine dose. Omicron breakthrough infection occurred in 71% of the vaccinees, enabling evaluation of vaccine- and vaccine/infection-induced hybrid immunity.
Results: Neutralizing antibodies were the highest against the ancestral D614G and were sequentially reduced against the Omicron variants BA.2, BA.5 and XBB.1.5. S1-specific IgG and neutralizing antibody levels were significantly higher in infected than in uninfected vaccinees, and the fourth vaccine dose in combination with a breakthrough infection resulted in high neutralizing antibody levels against all variants. T cell-mediated immunity, instead, was well retained already after two vaccine doses, and was not significantly strengthened by additional booster vaccine doses or Omicron breakthrough infections.
Discussion: While humoral immunity is sensitive to mutations in the S protein and thus declined rapidly, the cell-mediated immunity is durable to antigenic variation, which may explain the good efficacy of COVID-19 vaccines against a severe disease.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Belik, Reinholm, Kolehmainen, Heroum, Maljanen, Altan, Österlund, Laine, Ritvos, Pasternack, Naves, Iakubovskaia, Barkoff, He, Lempainen, Tähtinen, Ivaska, Jalkanen, Julkunen and Kakkola.)