Immune response and IgG subclass dynamics following repeated SARS-CoV-2 mRNA vaccination in Japanese healthcare workers.

In Japan, many healthcare workers received up to seven doses of SARS-CoV-2 mRNA vaccines by April 2024. While repeated vaccination aims to strengthen immunity, concerns about immune imprinting and IgG subclass switching, particularly to IgG4, have arisen. This study examined 19 healthcare workers who completed seven doses. Serum and PBMCs collected at five or three time points respectively to measure were analyzed for IgG subclasses, neutralizing antibodies and cellular responses. IgG1-3 levels declined after the second dose but recovered after the third, whereas IgG4 increased post-second dose and remained stable. Neutralizing antibodies against Omicron XBB.1.5 were undetectable after two doses but appeared after the third, despite all being Wuhan strain vaccines, and rose further after the sixth and seventh doses with updated formulations. Cellular immunity remained stable throughout. These findings indicate repeated mRNA vaccination enhances humoral immunity without progressive IgG4 elevation or additional cellular response boosts.