Omicron breakthrough infections after triple‐dose inactivated COVID‐19 vaccination: A comprehensive analysis of antibody and T‐cell responses

• Published in: Immunology Vol. 172; no. 2; pp. 313 - 327
• Main Authors: Xiang, Tiandan, Quan, Xufeng, Jia, Hang, Wang, Hua, Liang, Boyun, Li, Sumeng, Wang, Xiaoyan, Li, Huadong, Feng, Xuemei, Fan, Lei, Xu, Ling, Wang, Tong, Xiong, Shue, Yang, Dongliang, Liu, Jia, Zheng, Xin
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2024
• Subjects: Adult; Aged; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody response; Breakthrough Infections - epidemiology; Breakthrough Infections - immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; Deactivation; Female; Humans; Immune response; Immunization, Secondary; inactivated vaccine; Lymphocytes; Lymphocytes T; Male; Middle Aged; Neutralization; Omicron; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Spike protein; T-Lymphocytes - immunology; T‐cell response; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology; antibody response; inactivated vaccine; Omicron; COVID‐19; SARS‐CoV‐2; T‐cell response
• ISSN: 0019-2805; 1365-2567; 1365-2567
• DOI: 10.1111/imm.13764

This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS‐CoV‐2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post‐vaccination, SARS‐CoV‐2‐specific T‐cell responses, both CD4+ and CD8+, remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8+ T‐cell response, and the intensity of the spike protein‐specific T‐cell response was roughly comparable between WT and Omicron BA.5. Dynamic antibody responses against various COVID‐19 variants of concern (VOCs), following a triple‐dose regimen of the inactivated vaccine and subsequent breakthrough Omicron infection, are presented. The third dose of the inactivated vaccine demonstrated poor neutralization against Omicron. Antibody titres against most VOCs (WT, Alpha, Beta, and Delta) experienced a gradual decline. SARS‐CoV‐2‐specific CD4+ and CD8+ T‐cell responses remained notably stable over a one‐year follow‐up period. Breakthrough infections with Omicron significantly enhanced neutralization capabilities against various VOCs and enhanced the CD8+ T‐cell response.