Enhanced neutralizing antibody responses to rhinovirus c and age-dependent patterns of infection

Timothy Choi, Mark Devries, Leonard B. Bacharier, William Busse, Carlos A. Camargo, Robyn Cohen, Gregory P. Demuri, Michael D. Evans, 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 KercsmarHaejin Kim, Ingrid A. Laing, Petra LeBeau, Kristine E. Lee, Peter N. Le Souëf, Andrew Liu, David T. Mauger, Carole Ober, Tressa Pappas, Shilpa J. Patel, Wanda Phipatanakul, Jacqueline Pongracic, Christine Seroogy, Peter D. Sly, Christopher Tisler, Ellen R. Wald, Robert Wood, Ronald Gangnon, Daniel J. Jackson, Robert F. Lemanske, James E. Gern, Yury A. Bochkov

Research output: Contribution to journalArticlepeer-review


Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected muchless oftenthanRV-Aduring bothrespiratory illnesses andscheduled surveillance visits (P<0.001, x2) in older children. The prevalence of neutralizingantibodies toRV-AorRV-Ctypeswas low(5-27%) at the age of 2 years, but by the age of 16 years, RV-C seropositivity was more prevalent (78%vs. 18%for RV-A; P<0.0001). In the pooled analysis, the RV-C to RV-A detection ratio during illnesses was significantly related to age (P<0.0001), CDHR3 genotype (P<0.05), and wheezing illnesses (P<0.05). Furthermore, certain RV types (e.g., C2, C11, A78, and A12) were consistently more virulent and prevalent over time. Conclusions: Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.

Original languageEnglish (US)
Pages (from-to)822-830
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Issue number7
StatePublished - Apr 1 2021
Externally publishedYes

Bibliographical note

Funding Information:
Supported by the Environmental Influences on Child Health Outcomes program, Office of The Director, NIH, under award numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 (Person-Reported Outcome [PRO] Core), UG3/UH3 OD023282, and UG3/UH3 OD-023253; NIH grants R01AI148707, P01 HL070831, UM1 AI114271, R01 AI-114552, R01 AI-127507, U19 AI095227, UL1 RR024975, and R01-AI097172; the Sigrid Juselius Foundation, Helsinki, Finland; National Health and Medical Research Council grants 211912, 458513; and by grants APP1045760, APP1087700, APP1129996, APP1147630. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and other funding agencies.

Publisher Copyright:
© 2021 by the American Thoracic Society.


  • CDHR3
  • Epidemiology
  • Genetics
  • Rhinovirus
  • Wheezing


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