Cross-reactive antibody responses to coronaviruses elicited by SARS-CoV-2 infection or vaccination (preprint)

Background: The newly emerged SARS-CoV-2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID-19 vaccination or SARS-CoV-2 infection may boost cross-reactive antibodies to other human coronaviruses. Methods Pre- and post-vaccination sera from SARS-CoV-2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross-reactive antibodies raised against other human coronaviruses by enzyme-linked immunosorbent assay. In comparison, convalescent sera from COVID-19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS-CoV. Results Among SARS-CoV-2 infection naïve subjects, BNT or CV significantly increased the anti-S2 antibodies against Betacoronaviruses (OC43 and MERS-CoV) but not Alphacoronaviruses (229E). The pre-vaccination antibody response to the common cold human coronaviruses did not negatively impact the post-vaccination antibody response to SARS-CoV-2. Cross-reactive antibodies that binds to the S2 protein of MERS-CoV were similarly detected from the convalescent sera of COVID-19 patients with or without vaccination history. However, these anti-S2 antibodies do not possess neutralizing activity in MERS-CoV pseudoparticle neutralisation tests. Conclusions Our results suggest that SARS-CoV-2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero-epidemiological studies on MERS-CoV.

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after the third dose of BNT162b2 in healthy adolescents (preprint)

High effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 6 months after 2 doses, S IgG, S IgG Fc receptor-binding, S-RBD IgG and neutralizing antibody responses waned significantly, yet neutralizing antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, and PRNT50 against Omicron BA.2, as well as preserved cellular responses against BA.1 S. Sera from 100% and 96% of adolescents tested at 1 and 6 months after 2 doses could also neutralize BA.1. Based on PRNT50, we predict 92%, 89% and 68% effectiveness against COVID-19 with WT, BA.2 and BA.5 1 month after 3 doses. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after 3 doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

Long-Term Persistence of SARS-CoV-2 Neutralizing Antibody Responses After Infection and Estimates of the Duration of Protection (preprint)

The duration of immunity in SARS-CoV-2 infected people remains unclear. Neutralizing antibody responses are the best available correlate of protection against re-infection. Recent studies have estimated that the correlate of 50% protection from re-infection was 20% of the mean convalescent neutralizing antibody titre. We used sera collected from a cohort of 125 individuals with RT-PCR confirmed SARS-CoV-2 infections up to 386 days after symptom onset. In the subset of 65 sera collected from day 151 to 386 after symptom onset, all remained positive in 50% plaque reduction neutralization tests (PRNT50). Because antibody waning follows a bimodal pattern with slower waning beyond day 90 after illness, we fitted lines of decay to 115 sera from 62 patients collected beyond 90 after symptom onset and estimate that PRNT50 antibody will remain detectable for around 1,717 days after symptom onset and that 50% protective antibody titers will be maintained for around 990 days post-symptom onset, in symptomatic patients. Peak PRNT titres in mildly symptomatic children did not differ from those in mildly symptomatic adults but these antibody titres appear to wane faster in children. There was a high level of correlation between PRNT50 antibody titers and the % of inhibition in surrogate virus neutralization tests. We conclude that there will be relatively long-lived protection from re-infection following symptomatic COVID-19 disease.Funding Information: The study was supported by the Health and Medical Research Fund, Commissioned research on Novel Coronavirus Disease (COVID-19) (Reference no COVID190126) from the Food and Health Bureau, Hong Kong SAR Government and the Theme-based Research Scheme project no. T11-712/19-N, the University Grants Committee of the Hong Kong Government.Declaration of Interests: None of the authors have any conflicts of interest to declare.Ethics Approval Statement: Written informed consent was obtained from the participants or their parents (when the participant was a child) and the studies were approved by the institutional review boards of the respective hospitals, viz. Kowloon West Cluster (KW/EX-20-039 (144-27)), Kowloon Central / Kowloon East cluster (KC/KE-20-0154/ER2) and HKU/HA Hong Kong West Cluster (UW 20-273).