Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization

Yury A. Bochkov, Mark Devries, Kaitlin Tetreault, Ronald Gangnon, Sujin Lee, Leonard B. Bacharier, William W. Busse, Carlos A. Camargo, Timothy Choi, Robyn Cohen, Ramyani De, Gregory P. DeMuri, Anne M. Fitzpatrick, Peter J. Gergen, Kristine Grindle, Rebecca Gruchalla, Tina Hartert, Kohei Hasegawa, Gurjit K. Khurana Hershey, Patrick HoltKiara Homil, Tuomas Jartti, Meyer Kattan, Carolyn Kercsmar, Haejin Kim, Ingrid A. Laing, Peter N. Le Souëf, Andrew H. Liu, David T. Mauger, Tressa Pappas, Shilpa J. Patel, Wanda Phipatanakul, Jacqueline Pongracic, Christine Seroogy, Peter D. Sly, Christopher Tisler, Ellen R. Wald, Robert Wood, Robert F. Lemanske, Daniel J. Jackson, James E. Gern

Research output: Contribution to journalArticlepeer-review

Abstract

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer-lasting antibody responses compared with RV-A infections. We pooled RV diagnostic data from multiple studies of children with respiratory illnesses and compared the expected versus observed frequencies of sequential infections with RV-A or RV-C types using log-linear regression models. We tested longitudinally collected plasma samples from children to compare the duration of RV-A versus RV-C nAb responses. Our models identified limited reciprocal cross-neutralizing relationships for RV-A (A12–A75, A12–A78, A20–A78, and A75–A78) and only one for RV-C (C2–C40). Serologic analysis using reference mouse sera and banked human plasma samples confirmed that C40 infections induced nAb responses with modest heterotypic activity against RV-C2. Mixed-effects regression modeling of longitudinal human plasma samples collected from ages 2 to 18 years demonstrated that RV-A and RV-C illnesses induced nAb responses of similar duration. These results indicate that both RV-A and RV-C nAb responses have only modest cross-reactivity that is limited to genetically similar types. Contrary to our initial hypothesis, RV-C species may include even fewer cross-neutralizing types than RV-A, whereas the duration of nAb responses during childhood is similar between the two species. The modest heterotypic responses suggest that RV vaccines must have a broad representation of prevalent types.

Original languageEnglish
Article numbere29058
JournalJournal of Medical Virology
Volume95
Issue number8
DOIs
Publication statusPublished - Aug 2023

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