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

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.

Rhinovirus dynamics across different social structures

“…Instead, there was a turnover of the most prevalent types, which was likely influenced by temporal type dynamics. The disappearance of types after predominance at broad geographical scales was consistent with the development of long-term type-specific immunity 45 , 46 . A58 was identified as a frequent type in both the countrywide study (year 2014) and the subsequent HDSS study (year 2015/16), the recurring A58 viruses belonged to a different phylogenetic cluster.…”

Genomic epidemiology and evolution of rhinovirus in western Washington State, 2021-22

“…We found statistical association of some clusters with the year of detection which might indicate a possible relationship with the long-term immunity interference. While this clustering does not necessarily define antigenic and serotypic relatedness, it did cluster together RV-A12, RV-20, and RV-A78 which have previously shown cross-neutralizing protection [35].…”

“…However, this study emphasizes the importance of investigating correlations between genotypes and serotypes to understand longterm immunity and cross-protection. Recent research by Bochkov et al revealed crossprotection among some genetically similar genotypes in RV-A and RV-C species [35]. This fact was originally mentioned in 1982 when Cooney et al demonstrated cross-protection between 50 RV types, categorized them into 16 antigenic groups [36].…”

Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses

“…Despite the considerable sequence diversity of RV-C C-loops, we observed evidence of putative cross-reactivity at these sites bases on similar reactivity patterns between homologous C loops sequences. A recent study reported reciprocal cross-reactive neutralization between RV C2 and C40 in both mouse and human samples (Bochkov et al 2023). Our findings also grouped together RV C2 and C47 C-loops as putative cross-reactive epitopes indicating that potential cross-reactivity patterns can be deconvoluted from antibody binding profiles collected from peptide microarrays.…”