The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer-BioNTech Vaccine

The aim of this study was to analyze the profiles of IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare these profiles with those of non-infected immunocompetent or immunocompromised subjects that received two or more doses of an mRNA vaccine. The most notable findings from this study are as follows: (1) Convalescent subjects that were not hospitalized developed high and long-lasting antibody responses. (2) Both IgG1 and IgG3 subclasses were more prevalent in the SARS-CoV-2-infected population, whereas IgG1 was more prevalent after vaccination. (3) Individuals that were infected and then later received two doses of an mRNA vaccine exhibited a more robust neutralizing capacity against Omicron than those that were never infected and received two doses of an mRNA vaccine. (4) A class switch toward the "anti-inflammatory" antibody isotype IgG4 was induced a few weeks after the third dose, which peaked abruptly and remained at high levels for a long period. Moreover, the high levels of IgG4 were concurrent with high neutralizing percentages against various VOCs including Omicron. (5) Subjects with IBD also produced IgG4 antibodies after the third dose, although these antibody levels had a limited effect on the neutralizing capacity. Knowing that the mRNA vaccines do not prevent infections, the Omicron subvariants have been shown to be less pathogenic, and IgG4 levels have been associated with immunotolerance and numerous negative effects, the recommendations for the successive administration of booster vaccinations to people should be revised.