4.7 Article

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection

Journal

Publisher

AMER THORACIC SOC
DOI: 10.1164/rccm.202010-3753OC

Keywords

rhinovirus; genetics; wheezing; CDHR3; epidemiology

Funding

  1. NCATS NIH HHS [UL1 TR001422] Funding Source: Medline
  2. NCRR NIH HHS [UL1 RR024975, TL1 RR024978] Funding Source: Medline
  3. NHLBI NIH HHS [P01 HL070831] Funding Source: Medline
  4. NIAID NIH HHS [R01 AI097172, UM2 AI117870, UM1 AI114271, U19 AI095227, R01 AI148707, R01 AI114552, U19 AI104317, R01 AI127507] Funding Source: Medline
  5. NIH HHS [UH3 OD023282, UG3 OD023253, U2C OD023375, UH3 OD023253, UG3 OD023282, U24 OD023382, U24 OD023319] Funding Source: Medline

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This study analyzed longitudinal data to investigate the impact of age and other factors on susceptibility to RV-C infections. The results showed that while RV-A and RV-C infections were similar in infancy, RV-C detection decreased with age while neutralizing antibody prevalence increased. The ratio of RV-C to RV-A detection during illnesses was found to be related to age, genetics, and wheezing illnesses, indicating potential factors influencing susceptibility to RV-C.
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 often than RV-A during both respiratory illnesses and scheduled surveillance visits (P < 0.001, chi(2)) in older children. The prevalence of neutralizing antibodies to RV-A or RV-C types was 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.

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