Epidemiology, immunology, and evolution of SARS-CoV-2 and other coronaviruses before and during the COVID-19 pandemic

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Immunity to endemic coronaviruses and SARS-CoV-2 before and during the COVID-19 pandemic in children in Cebu, Philippines. NIAID and University of the Philippines Manila are collaborating to study SARS-CoV-2 and endemic coronavirus seroprevalence in children in the Central Visayas Region in the Philippines. In this region, numerous variants of concern now circulate but little is known about the infection and disease risk for SARS-CoV-2. This study is part of an ongoing longitudinal cohort of children 12-17 years of age and residing in Bogo and Balamban participating in the study entitled "Effect of baseline dengue serostatus among tetravalent dengue vaccine CYD-TDV (Dengvaxia) recipients on subsequent virologically confirmed dengue in the Philippines". This cohort provides a unique opportunity to interrogate immunity induced by endemic coronaviruses prior to the start of the COVID-19 pandemic (late 2019/early 2020) and follow the same children over the course of the pandemic (2020 and 2021). We have used ELISAs and epidemiological methods to measure serum antibodies to the receptor binding domains and spike antigens of SARS-CoV-2, OC43, HKU1, 229E, and NL63. Effect of sequential exposure on breadth of immunity to SARS-CoV-2 variants. The rapid emergence of new SARS-CoV-2 variants challenges vaccination strategies. In collaboration with teams at the FDA and USU, we characterized the antigenic diversity among SARS-CoV-2 variants following single and multiple exposures in longitudinal infection and vaccine cohorts. We made antigenic maps for primary infection neutralization titers and showed that BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and are more similar to the Beta/Mu/Gamma cluster. Further, we found that three doses of an mRNA COVID-19 vaccine increased neutralization recognition of BA.1 more than BA.4/BA.5 or BA.2.12.1. We used a related technique called an antibody landscape to show that Omicron BA.1/BA.1.1 post-vaccination infection (PVI) elicited more balanced neutralization of distinct variants than three doses alone, including to unexposed variants, although with a smaller gain than expected to BA.2.12.1 and BA.4/BA.5. Those with BA.1/BA1.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic breadth. Overall, our analyses accounting for antigenic differences among variants of concern when interpreting neutralization titers aids understanding of complex patterns in humoral immunity and informs selection of future COVID-19 vaccine strains. Preprint: Wang W, Lusvarghi S, Subramanian R, Epsi NJ, Wang R, Goguet E, Fries AC, Echegaray F, Vassell R, Coggins SA, Richard SA, Lindholm DA, Mende K, Ewers E, Larson D, Colombo RE, Colombo C, Joseph JO, Rozman J, Smith A, Lalani T, Berjohn C, Maves R, Jones M, Mody R, Huprikar N, Livezey J, Saunders D, Hollis-Perry M, Wang G, Ganesan A, Simons MP, Broder CC, Tribble D, Laing ED, Agan B, Burgess TH, Mitre E, Pollett SD*, Katzelnick LC*, Weiss CD*. Post-vaccination Omicron infections induce broader immunity across antigenic space than prototype mRNA COVID-19 booster vaccination or primary infection. bioRxiv. Posted July 06, 2022. doi: 10.1101/2022.07.05.498883. *Corresponding authors.