Inactivated vaccine fueled adaptive immune responses to Omicron in 2-year COVID-19 convalescents

Abstract For nearly three years, humans have experienced multiple rounds of global transmission of SARS-CoV-2 and its variant strains. In addition, the widely used vaccines against SARS-CoV-2 involve multiple strategies of development and inoculation, globally. Thus, the acquired immunity established among humans is quite complicated, and there is still a lack of understanding within a panoramic vision. Here, we provide the special characteristics of the cellular and humoral immune responses in 2-year convalescents after the inoculation of inactivated vaccine, in parallel to vaccinated COVID-19 naïve persons and unvaccinated controls. The decreasing trends of the IgG, IgA, and neutralizing antibodies (NAb), but not IgM of the convalescents were reversed by the vaccination. Both cellular and humoral immunity to SARS-CoV-2 in convalescents after vaccination were higher than the vaccinated COVID-19 naïve persons. Notably, the inoculation of inactivated vaccine fueled the NAb to Omicron BA.1, BA.2, BA.4, and BA.5 in the 2-year convalescents, much higher than the NAb during 6 months and 1 year after symptoms onset. And no obvious T cell escaping to the S protein was observed after the inoculation in the 2-year convalescents. The study provides insight into the complicated features of acquired immunity of humans to SARS-CoV-2 and variants in the real world, and indicated that promoting vaccine inoculation is an essential way to achieve herd immunity against emerging viral variants for the ongoing COVID-19 pandemic, including the convalescents.