Straus, S. E. | bioRxiv Science

bioRxiv2024

Urban wastewater contains a functional human antibody repertoire of mucosal origin

Wastewater-based surveillance of human disease offers timely insights to public health, helping to mitigate infectious disease outbreaks and decrease downstream morbidity and mortality. These systems rely on nucleic acid amplification tests for monitoring disease trends, while antibody-based seroprevalence surveys gauge community immunity. However, serological surveys are resource-intensive and subject to potentially long lead times and sampling bias. We identified and characterized a human antibody repertoire, predominantly secretory IgA, isolated from a central wastewater treatment plant and building-scale wastewater collection points. These antibodies partition to the solids fraction and retain immunoaffinity for SARS-CoV-2 and Influenza A virus antigens. This stable pool could enable real-time tracking of correlates of vaccination, infection, and immunity, aiding in establishing population-level thresholds for immune protection and assessing the efficacy of future vaccine campaigns, particularly those that are designed to induce humoral mucosal immunity.

immunology↗

bioRxiv2022

Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron variants

The omicron variant of concern (VOC) of SARS-CoV-2 was first reported in November 2021 in Botswana and South Africa. Omicron has evolved multiple mutations within the spike protein and the receptor binding domain (RBD), raising concerns of increased antibody evasion. Here, we isolated infectious omicron from a clinical specimen obtained in Canada. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2, beta, delta, and omicron VOCs was assessed. Convalescent sera from unvaccinated individuals infected by the ancestral virus during the first wave of COVID-19 in Canada (July, 2020) demonstrated reduced neutralization against beta and omicron VOCs. Convalescent sera from unvaccinated individuals infected by the delta variant (May-June, 2021) neutralized omicron to significantly lower levels compared to the delta variant. 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. Importantly, infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron. This data will inform current booster vaccination strategies, and we highlight the need for additional studies to identify longevity of immunity against SARS-CoV-2 and optimal neutralizing antibody levels that are necessary to prevent infection and/or severe COVID-19.

immunology↗