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 Holt; Kiara 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 Jr; Daniel J Jackson; James E Gern; program collaborators for Environmental influences on Child Health Outcomes

doi:10.1002/jmv.29058

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

J Med Virol. 2023 Aug;95(8):e29058. doi: 10.1002/jmv.29058.

Authors

Yury A Bochkov¹, Mark Devries¹, Kaitlin Tetreault¹, Ronald Gangnon¹, Sujin Lee², Leonard B Bacharier³, William W Busse¹, Carlos A Camargo⁴, Timothy Choi¹, Robyn Cohen⁵, Ramyani De², Gregory P DeMuri¹, Anne M Fitzpatrick⁶, Peter J Gergen⁷, Kristine Grindle¹, Rebecca Gruchalla⁸, Tina Hartert³, Kohei Hasegawa⁴, Gurjit K Khurana Hershey⁹, Patrick Holt¹⁰, Kiara Homil¹¹, Tuomas Jartti^{11

12}, Meyer Kattan¹³, Carolyn Kercsmar⁹, Haejin Kim¹⁴, Ingrid A Laing¹⁵, Peter N Le Souëf¹⁵, Andrew H Liu¹⁶, David T Mauger¹⁷, Tressa Pappas¹, Shilpa J Patel¹⁸, Wanda Phipatanakul¹⁹, Jacqueline Pongracic²⁰, Christine Seroogy¹, Peter D Sly²¹, Christopher Tisler¹, Ellen R Wald¹, Robert Wood²², Robert F Lemanske Jr¹, Daniel J Jackson¹, James E Gern¹; program collaborators for Environmental influences on Child Health Outcomes

Affiliations

¹ University of Wisconsin-Madison, Madison, Wisconsin, USA.
² Department of Pediatrics, Center for ViroScience and Cure, Emory University School of Medicine, Atlanta, Georgia‎, USA.
³ Vanderbilt University, Nashville, Tennessee, USA.
⁴ Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁵ Boston University, Boston, Massachusetts, USA.
⁶ Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
⁷ National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland, USA.
⁸ University of Texas Southwestern, Dallas, Texas, USA.
⁹ Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
¹⁰ Telethon Kids Institute, The University of Western Australia, Perth, Australia.
¹¹ University of Turku and Turku University Hospital, Turku, Finland.
¹² PEDEGO Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland.
¹³ Columbia University, New York, New York, USA.
¹⁴ Henry Ford Health Systems, Detroit, Michigan, USA.
¹⁵ University of Western Australia, Perth, Australia.
¹⁶ Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA.
¹⁷ Penn State University, Hershey, Pennsylvania, USA.
¹⁸ George Washington University, Washington, DC, USA.
¹⁹ Harvard Medical School, Boston, Massachusetts, USA.
²⁰ Northwestern University, Chicago, Illinois, USA.
²¹ Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia.
²² Johns Hopkins University, Baltimore, Maryland, USA.

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.

Keywords: cross-neutralization; duration; neutralizing antibodies; rhinovirus; vaccine.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibodies, Neutralizing
Antibody Formation
Asthma*
Child
Child, Preschool
Cross Reactions
Humans
Mice
Rhinovirus*

Substances

Antibodies, Neutralizing

Abstract

Publication types

MeSH terms

Substances

Grants and funding