SARS-CoV-2 Omicron infection augments the magnitude and durability of systemic and mucosal immunity in triple-dose CoronaVac recipients

Abstract

The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4 + and CD8 + T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4 + T cells, and memory CD8 + T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection. IMPORTANCE There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection. CLINICAL TRIAL This study is registered with ClinicalTrials.gov as NCT05680896 .

SARS-CoV-2 Humoral and Cellular Immune Responses in HIV-Positive Patients

“…Noteworthy, in the present study, SARS-CoV-2 anti-S IgA antibodies, a surrogate marker for local immunity, were still present in most PLWH at 8 -9 months after infection or vaccination; similar to the data reported in longitudinal follow-up studies in the general population, showing persistent adaptative systemic and local immune responses up to two years, with more durable and organized immune responses after recovery from COVID-19 [37]. Recent studies have also demonstrated that breakthrough infections with the currently circulating Omicron variants enhance both the breadth and persistence of all types of specific immune responses, including nasal spike-specific IgA levels [42]. Longitudinal studies have also demonstrated a rapid activation of SARS-CoV-2 specific cellular immune responses during breakthrough infections, explained both by the recall of CD4+ and CD8+ spike-specific memory cells, and de novo T cell responses [43].…”

SARS-CoV-2 Humoral and Cellular Immune Responses in People Living with HIV

“…Noteworthy, in the present study, SARS-CoV-2 anti-S IgA antibodies, a surrogate marker for local immunity, were still present in most PLWH at 8–9 months after infection or vaccination, similar to the data reported in longitudinal follow-up studies in the general population, showing persistent adaptative systemic and local immune responses up to two years, with more durable and organized immune responses after recovery from COVID-19 [ 38 ]. Recent studies have also demonstrated that breakthrough infections with the currently circulating Omicron variants enhance both the breadth and persistence of all types of specific immune responses, including nasal spike-specific IgA levels [ 43 ]. Longitudinal studies have also demonstrated a rapid activation of SARS-CoV-2-specific cellular immune responses during breakthrough infections, explained both by the recall of CD4+ and CD8+ spike-specific memory cells and de novo T cell responses [ 44 ].…”