Immune Imprinting Drives Human Norovirus Potential for Global Spread
Lisa C. Lindesmith, Florencia A. T. Boshier, Paul D. Brewer-Jensen, Sunando Roy, Verónica Costantini, Michael L. Mallory, Mark R. Zweigart, Samantha R. May, Helen Conrad, Kathleen O’Reilly, Daniel Kelly, Cristina Celma, Stuart Beard, Rachel Williams, Helena J. Tutill, Sylvia Becker‐Dreps, Filemón Bucardo, David J. Allen, Jan Vinjé, Richard A. Goldstein, Judith Breuer, Ralph S. Baric
Abstract
In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults.