The appearance of anti-spike receptor binding domain immunoglobulin G4 responses after repetitive immunization with messenger RNA-based COVID-19 vaccines

• Published in: International journal of infectious diseases Vol. 139; pp. 1 - 5
• Main Authors: Yoshimura, Michinobu, Sakamoto, Atsuhiko, Ozuru, Ryo, Kurihara, Yusuke, Itoh, Ryota, Ishii, Kazunari, Shimizu, Akinori, Chou, Bin, Nabeshima, Shigeki, Hiromatsu, Kenji
• Format: Journal Article
• Language: English
• Published: Canada Elsevier 01-02-2024
• Subjects: Antibodies, Viral; Breakthrough infection; Breakthrough Infections; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Humans; IgG subclass; IgG4; Immunization; Immunoglobulin G; mRNA vaccine; RNA, Messenger - genetics; SARS-CoV-2; Vaccination; COVID-19; IgG4; SARS-CoV-2; IgG subclass; Breakthrough infection; mRNA vaccine
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2023.11.028

It is crucial to analyze the consequences of repeated messenger RNA (mRNA)-based COVID-19 vaccinations on SARS-CoV-2 spike receptor binding domain (RBD)-specific immunoglobulin (Ig)G subclass and the possible causal relationship with breakthrough infection.
We examined the longitudinal kinetics of RBD-specific IgG subclass antibodies in sera after receiving the second, third, and fourth doses of mRNA-based COVID-19 vaccines in Japanese healthcare workers. Anti-RBD IgG subclass in sera of patients with COVID-19-infected who had not received the COVID-19 vaccine were also examined. We compared anti-RBD IgG subclass antibody titers in the serum of pre-breakthrough-infected vaccinees and non-infected vaccinees.
The seropositivity of anti-RBD IgG4 after the vaccination was 6.76% at 1 month after the second dose, gradually increased to 50.5% at 6 months after the second dose, and reached 97.2% at 1 month after the third dose. The seropositivity and titers of anti-RBD IgG1/IgG3 quickly reached the maximum at 1 month after the second dose and declined afterward. The elevated anti-RBD IgG4 Ab levels observed after repeated vaccinations were unlikely to increase the risk of breakthrough infection.
Repeated vaccinations induce delayed but drastic increases in anti-RBD IgG4 responses. Further functional investigations are needed to reveal the magnitude of the high contribution of spike-specific IgG4 subclasses after repeated mRNA-based COVID-19 vaccinations.