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 & patents

Abstract

TRACKING SARS-COV-2 ANTIGENIC EVOLUTION AND EFFECTS ON COVID-19 VACCINES SARS-CoV-2 rapidly diversified into distinct variants with modified epitopes targeted by neutralizing antibodies. RNA viruses have exceptionally high mutation rates that enable rapid evolution. Selection driven by immunological pressure in previously infected hosts is an important factor in the evolution of numerous viruses. However, techniques to relate antigenic features to these evolutionary patterns remain limited. Our lab specializes in antigenic cartography, a technique to characterize virus relatedness based on how they are neutralized. Sera that have each have been ‘trained’ on different versions of the viral epitopes are titrated by neutralization assay against diverse viruses. Antigenic cartography uses multidimensional scaling to convert titers to antigenic distances, creating a map in as low of dimensional space as can accurately fit the dataset. Antigenic cartography requires primary infection antisera, which became increasingly difficult to find later in the COVID-19 pandemic. Model animal sera have been used to antigenically characterize influenza, and other work suggests hamsters may be an appropriate model. In collaboration with USU and the FDA, we made antigenic maps of SARS-CoV-2 variants with both human and hamster primary infection antisera. We showed that neutralizing antibody titers for human and hamster sera produce similar antigenic maps and distances among viruses. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. We used antibody landscapes to evaluate multi-exposure antibody responses and show that compared to after ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, the XBB.1.5 booster resulted in the broadest neutralization of XBB sub-lineage variants. This work provides insight into into the antigenic evolution of SARS-CoV-2, how changes affected neutralization breadth in those with multiple exposures, and how model animal sera can be used to continue surveilling SARS-CoV-2 evolution. - Wang W, Bhushan G, Paz S, Stauft CB, Selvaraj P, Goguet E, Bishop-Lilly KA, Subramanian R, Vassell R, Lusvarghi S, Cong Y, Agan B, Richard SA, Epsi NJ, Fries A, Fung CK, Conte MA, Holbrook MR, Wang TT, Burgess TH, Pollett SD, Mitre E, Katzelnick LC, Weiss CD. Human and hamster sera correlate well in identifying antigenic drift among SARS-CoV-2 variants, including JN.1. Journal of Virology. 2024; 98(11): e0094824. COMPARISON OF DENGUE AND SARS-COV-2 CELLULAR IMMUNITY We are comparing dengue virus-specific cellular responses after natural infection and vaccination to the resting cellular response to SARS-CoV-2, a pathogen to which nearly all the participants in our ongoing dengue vaccine trial have been exposed multiple times either by natural infection or vaccination over the COVID-19 pandemic. This will allow us to test if repeat exposure to dengue virus induces similar cellular immune profiles and B cell receptor mutational frequencies to those observed against SARS-CoV-2, providing further insights into the induction of broad anti-viral protective immunity against emerging viral diseases.