IFN-γ mediated-cellular immunity is essential to the vaccine-induced protection against SARS-CoV-2 (preprint)

Mass vaccination schemes have been launched for COVID-19 worldwide. However, recent studies have revealed that SARS-CoV-2 Omicron and its sub-lineages efficiently evade humoral immunity from vaccination or previous infection. Therefore, it is of great importance to investigate the contribution of cellular immunity against infection of emerging variants of SARS-CoV-2 in the context of vaccine-induced immunity. By using C57BL/6J and K18-hACE2 mouse models, we demonstrated that BNT162b2 induces robust protective immunity in B-cell deficient (μMT) mice. We further demonstrated that this protection is attributed to the cellular immunity mediated by robust IFN-γ production. In addition, we revealed that SARS-CoV-2 Omicron BA.1 could also induce strong cellular responses in vaccinated μMT mice upon viral challenge, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants that evade antibody-mediated immunity. Overall, our study provides evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies.

Improved detection of antibody against SARS-CoV-2 by microsphere-based antibody assay (preprint)

Objective: Currently available COVID-19 antibody tests using enzyme immunoassay (EIA) or immunochromatographic assay have variable sensitivity and specificity. Here, we developed and evaluated a novel microsphere-based antibody assay (MBA) for the detection of immunoglobulin G (IgG) against SARS-CoV-2 nucleoprotein (NP) and spike protein receptor binding domain (RBD). Method: We developed a microsphere-based assay (MBA) to determine the levels of IgG against SARS-CoV-2 NP and spike RBD. The seropositive cut-off mean fluorescent intensity (MFI) was set using a cohort of 294 anonymous serum specimens collected in 2018. The specificity was assessed using serum specimens collected from organ donors or influenza patients before 2020. Seropositive rate was determined among patients with COVID-19. Time-to-seropositivity and signal-to-cutoff (S/CO) ratio were compared between MBA and EIA. Results: MBA had a specificity of 100% (93/93; 95% confidence interval [CI], 96-100%) for anti-NP IgG and 98.9% (92/93; 95% CI 94.2-100%) for anti-RBD IgG. The MBA seropositive rate for convalescent serum specimens of COVID-19 patients were 89.8% (35/39) for anti-NP IgG and 79.5% (31/39) for anti-RBD IgG. The time-to-seropositivity was shorter with MBA than that of EIA. When compared with EIA, MBA could better differentiate between COVID-19 patients and negative controls with significantly higher S/CO ratio for COVID-19 patients and lower S/CO ratio with negative controls. MBA also had fewer specimens in the equivocal range (S/CO 0.9-1.1) than EIA. Conclusion: MBA is robust and simple, and is suitable for clinical microbiology laboratory for the accurate determination of anti-SARS-CoV-2 antibody for retrospective diagnosis, serosurveillance, and vaccine trials.