Abstract
Waned vaccine-induced immunity and emerging severe acute respiratory syndrome coronavirus 2 variants with potential for immune escape pose a major threat to the coronavirus disease (COVID-19) pandemic. Here, we showed that humoral immunity components, including anti-S + N, anti-RBD IgG, and neutralizing antibodies (NAbs), gradually waned and decreased the neutralizing capacity against emerging Omicron variants at 3 and 6 months after two inactivated COVID-19 vaccinations. We evaluated two boosting strategies with either a third dose of inactivated vaccine (homologous, I-I-I) or a recombinant subunit vaccine (heterologous, I-I-S). Both strategies induced the production of high levels of NAbs with a broad neutralizing capacity and longer retention. Interestingly, I-I-S induced 3.5-fold to 6.8-fold higher NAb titres than I-I-I, with a broader neutralizing capacity against six variants of concern, including Omicron. Further immunological analysis revealed that the two immunization strategies differ considerably, not only in the magnitude of total NAbs produced, but also in the composite pattern of NAbs and the population of virus-specific CD4+ T cells produced. Additionally, in some cases, heterologous boosted immunity induced the production of more effective epitopes than natural infection. The level of I-I-S-induced NAbs decreased to 48% and 18% at 1 and 3 months after booster vaccination, respectively. Overall, our data provide important evidence for vaccination strategies based on available vaccines and may help guide future global vaccination plans.
Keywords: COVID-19 vaccine; T cell response; heterologous boosting; inactivated vaccine; neutralizing antibody; prime-boost strategy; subunit vaccine.
【저자키워드】 neutralizing antibody, COVID-19 vaccine, Inactivated vaccine, T cell response, Subunit vaccine., heterologous boosting, prime-boost strategy, 【초록키워드】 COVID-19, coronavirus disease, neutralizing antibody, Vaccine, coronavirus, COVID-19 vaccine, vaccination, pandemic, Immunity, Neutralizing antibodies, T cells, variant, variants of concern, omicron, Epitopes, Humoral immunity, T cell, Immune escape, Inactivated vaccine, Vaccination strategies, Subunit vaccine, Neutralizing, neutralizing capacity, respiratory, natural infection, homologous, epitope, T cell response, CD4+ T cell, Heterologous, inactivated, NAb, booster vaccination, Evidence, Analysis, dose, Vaccine-induced immunity, Vaccination strategy, Anti-RBD IgG, in some, acute respiratory syndrome, composite pattern, subunit, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, components, NAbs, help, RBD IgG, titre, anti-S, COVID-19 vaccinations, immunological, effective, immunization strategy, produced, evaluated, magnitude, waned, 【제목키워드】 Vaccine, Immunity, variant, dose, acute respiratory syndrome, subunit, increase,