Omicron BA.1 breakthrough infections in inactivated COVID-19 vaccine recipients induced distinct pattern of antibody and T cell responses to different Omicron sublineages

Emerg Microbes Infect. 2023 Dec;12(1):2202263. doi: 10.1080/22221751.2023.2202263.

Abstract

The adaptive immunity against SARS-CoV-2 prototype strain and Omicron sublineages induced by BA.1 breakthrough infection in vaccinees of inactivated COVID-19 vaccines have not been well characterized. Here, we report that BA.1 breakthrough infection induced mucosal sIgA and resulted in higher IgG titers against prototype strain and Omicron sublineages in vaccinees than in vaccine naïve-infected individuals. BA.1 breakthrough infection boosted antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis to prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.2.75 but not BA.4/5 and induced neutralization against prototype strain and BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5 but not BF.7, BQ.1, and XBB. In total, BA.1 breakthrough infection individuals produced less extensive sIgA, plasma IgG and NAb responses against Omicron sublineages compared with those against prototype strain. Further, BA.1 breakthrough infection induced recall B cell response to prototype strain and Omicron variant, primarily targeting memory B cells producing conserved epitopes. Memory T cell responses against Omicron is largely preserved. Individuals with vaccine booster did not induce more beneficial immune responses to Omicron sublineages upon BA.1 breakthrough infection than those with primary vaccine dose only. The breakthrough infection individuals produced stronger adaptive immunity than those of inactivated vaccine-healthy individuals. These data have important implications for understanding the vaccine effectiveness and adaptive immunity to breakthrough infection in individuals fully immunized with inactivated vaccines. Omicron sublineages, especially for those emerged after BA.4/5 strain, evade NAb responses induced by BA.1 breakthrough infection. It is urgent to optimize the vaccine immunogen design and formulations to SARS-CoV-2 variants.

Keywords: Omicron sublineages; SARS-CoV-2; breakthrough infection; cellular immune responses; humoral immune responses.

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Breakthrough Infections
  • COVID-19 Vaccines*
  • COVID-19*
  • Humans
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • SARS-CoV-2
  • T-Lymphocytes

Substances

  • COVID-19 Vaccines
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Antibodies, Viral
  • Antibodies, Neutralizing

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This study was funded by Beijing Natural Science Foundation (L222055), Science Fund for Creative Research Groups of the National Natural Science Foundation of China (82221004), the National Natural Science Foundation (81930063, 81890990), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-047, 2021-I2M-1-038, 2018-I2M-2-002), Haihe Laboratory of Cell Ecosystem Innovation Fund (22HHXBSS00001), the Fundamental Research Funds for the Central Universities for Peking Union Medical College (3332021092, 3332021093), UK Medical Research Council, the National Program on Key Research Project of China (2021YFA1100900). We are grateful to all individuals who participated in this study and their families. This manuscript was edited at Life Science Editors.