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

Yury A. Bochkov, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Mark Devries, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Kaitlin Tetreault, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Ronald Gangnon, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sujin Lee, Department of Pediatrics, Center for ViroScience and Cure, Emory University School of Medicine, Atlanta, Georgia‎, USA.
Leonard B. Bacharier, Vanderbilt University, Nashville, Tennessee, USA.
William W. Busse, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Carlos A. Camargo, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
Timothy Choi, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Robyn Cohen, Boston University, Boston, Massachusetts, USA.
Ramyani De, Department of Pediatrics, Center for ViroScience and Cure, Emory University School of Medicine, Atlanta, Georgia‎, USA.
Gregory P. DeMuri, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Anne M. Fitzpatrick, Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Peter J. Gergen, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland, USA.
Kristine Grindle, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Rebecca Gruchalla, University of Texas Southwestern, Dallas, Texas, USA.
Tina Hartert, Vanderbilt University, Nashville, Tennessee, USA.
Kohei Hasegawa, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
Gurjit K. Khurana Hershey, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Patrick Holt, Telethon Kids Institute, The University of Western Australia, Perth, Australia.
Kiara Homil, University of Turku and Turku University Hospital, Turku, Finland.
Tuomas Jartti, University of Turku and Turku University Hospital, Turku, Finland.
Meyer Kattan, Columbia University, New York, New York, USA.
Carolyn Kercsmar, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Haejin Kim, Henry Ford Health Systems, Detroit, Michigan, USA.
Ingrid A. Laing, University of Western Australia, Perth, Australia.
Peter N. Le Souëf, University of Western Australia, Perth, Australia.
Andrew H. Liu, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA.
David T. Mauger, Penn State University, Hershey, Pennsylvania, USA.
Tressa Pappas, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Shilpa J. Patel, George Washington University, Washington, DC, USA.
Wanda Phipatanakul, Harvard Medical School, Boston, Massachusetts, USA.

Document Type

Journal Article

Publication Date

8-1-2023

Journal

Journal of medical virology

Volume

95

Issue

8

DOI

10.1002/jmv.29058

Keywords

cross-neutralization; duration; neutralizing antibodies; rhinovirus; vaccine

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.

Department

Pediatrics

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