Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, Beta, Delta, and Omicron variants.

Background: SARS-CoV-2 Omicron variant of concern (VOC) has evolved multiple mutations within the spike protein, raising concerns of increased antibody evasion. In this study, we assessed the neutralization potential of COVID-19 convalescent sera and sera from vaccinated individuals against ancestral SARS-CoV-2 and VOCs. Methods: The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2 and Beta, Delta, and Omicron VOCs was assessed using a micro-neutralization assay. Findings: Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against Beta and Omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the Omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the Delta variant, was not sufficient to induce high neutralizing antibody titers against Omicron. Conclusions: In summary, we demonstrate that convalescent and vaccinated sera display varying levels of SARS-CoV-2 VOC neutralization. Data from this study will inform booster vaccination strategies against SARS-CoV-2 VOCs. Funding: This research was funded by the Canadian Institutes of Health Research (CIHR). VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility.

Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection.

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2-4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission.