The COVID-19 pandemic, caused by SARS-CoV-2, continues to pose a global health threat. The emergence of numerous variants, including Alpha, Beta, Gamma, Kappa, Delta, and Omicron, has raised concerns about immune evasion and reinfection, even in individuals who have recovered from COVID-19. The immune response to SARS-CoV-2 involves both antibodies and T cells, with antibodies playing a crucial role in preventing reinfection. However, studies have shown that antibody responses wane over time after recovery, and T cell responses may also decline. Vaccination is essential to bolster immunity against SARS-CoV-2 and its variants. Various COVID-19 vaccines have been developed, including mRNA and inactivated vaccines. While the impact of mRNA vaccines on recovered patients has been studied, research on inactivated vaccines is limited. This study aimed to evaluate the efficacy of inactivated COVID-19 vaccines in boosting humoral and cellular immune responses in recovered patients and their ability to neutralize various SARS-CoV-2 variants.

Existing literature highlights the waning immunity in recovered COVID-19 patients, making them susceptible to reinfection, particularly by variants like Omicron. Studies have shown that SARS-CoV-2-specific antibodies are essential for protection against reinfection, but their levels decline months after recovery. While T cell immunity may persist longer, its function can be compromised over time. The development and deployment of various COVID-19 vaccines, including mRNA and inactivated vaccines, represent a crucial strategy to combat the pandemic. Previous research on mRNA vaccines has demonstrated their effectiveness in enhancing immune responses in recovered patients. However, data on the effects of inactivated vaccines in this population were limited prior to this study.

This study recruited 448 recovered COVID-19 patients in Wuhan, China. Participants were divided into two groups: an infection-only group (47 unvaccinated patients) and a hybrid-immunity group (401 vaccinated patients). The hybrid-immunity group received one, two, or three doses of one of several inactivated COVID-19 vaccines. Serum samples were collected to measure IgG antibody titers against the receptor-binding domain (RBD) and nucleocapsid protein (NP) of SARS-CoV-2 using ELISA. Neutralization assays, using both pseudotyped and authentic viruses, were conducted to determine the neutralizing antibody (NAb) titers against the Wuhan-Hu-1, Delta, and Omicron variants. Peripheral blood mononuclear cells (PBMCs) were used to assess SARS-CoV-2-specific CD4+ T cell responses via intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays. The study analyzed the changes in antibody and T cell responses over time, comparing the vaccinated group to the unvaccinated group.

Vaccination significantly increased the geometric mean titers (GMTs) of RBD-IgG and NP-IgG antibodies in recovered patients compared to unvaccinated individuals. The neutralizing antibody activity against the Wuhan-Hu-1, Delta, and Omicron variants was also significantly higher in the vaccinated group, persisting for up to 9 months post-vaccination. Although the humoral response decreased over time, and Omicron exhibited greater resistance to neutralization compared to other variants, the overall neutralizing capacity remained significantly elevated in the vaccinated group. Furthermore, vaccination boosted the intensity of SARS-CoV-2-specific CD4+ T cell responses in recovered patients. The study found no significant difference in the immune response based on the number of vaccine doses received (one, two, or three doses). There was a positive correlation between RBD-IgG and NP-IgG titers, but no correlation was found between antibody levels and factors such as disease severity, age, or sex.

The findings of this study demonstrate the significant benefit of inactivated COVID-19 vaccines in boosting both humoral and cellular immunity against SARS-CoV-2 in previously infected individuals. The enhanced antibody titers and neutralizing activity provide improved protection against reinfection and the emergence of new variants. While the waning antibody response over time and the greater resistance of Omicron to neutralization highlight the need for continued monitoring and potential booster strategies, this study clearly shows that inactivated vaccines enhance long-term immunity in recovered patients. The results underscore the crucial role of vaccination in controlling the COVID-19 pandemic.

This study provides strong evidence for the effectiveness of inactivated COVID-19 vaccines in significantly boosting the immune response in recovered patients. The enhanced antibody and T cell responses offer substantial protection against reinfection and various SARS-CoV-2 variants. Further research could investigate the long-term durability of these enhanced immune responses and explore the optimal vaccination strategies to maintain high levels of protection against emerging variants.

The study was conducted in a single geographic location (Wuhan, China), which may limit the generalizability of the findings to other populations. The limited sample size of the infection-only group could also affect the statistical power of some comparisons. Additionally, the study focused primarily on humoral and CD4+ T cell responses, with limited analysis of other immune components such as B cells and CD8+ T cells.