Rhinovirus Biology, Antigenic Diversity, and Advancements in the Design of a Human Rhinovirus Vaccine

Abstract

Human rhinovirus (HRV) remains a leading cause of several human diseases including the common cold. Despite considerable research over the last 60 years, development of an effective vaccine to HRV has been viewed by many as unfeasible due, in part, to the antigenic diversity of circulating HRVs in nature. Over 150 antigenically distinct types of HRV are currently known which span three species: HRV A, HRV B, and HRV C. Early attempts to develop a rhinovirus vaccine have shown that inactivated HRV is capable of serving as a strong immunogen and inducing neutralizing antibodies. Yet, limitations to virus preparation and recovery, continued identification of antigenic variants of HRV, and logistical challenges pertaining to preparing a polyvalent preparation of the magnitude required for true efficacy against circulating rhinoviruses continue to prove a daunting challenge. In this review, we describe HRV biology, antigenic diversity, and past and present advances in HRV vaccine design.

Keywords: common cold; respiratory disease; rhinovirus; vaccine; viral diversity.

FIGURE 1

Human rhinovirus genomic organization, virion structure, and species. (A) The 7.21 kb +ssRNA genome of HRV-16 is comprised of a single open-reading frame encoding 11 gene products, which upon translation into three distinct polyproteins are cleaved by HRV-encoded proteases (2A and 3C). The 5′-end of the genome is capped with a short viral priming protein (VPg) for incorporation during virion assembly and a the 3′-end is polyadenylated. Capsid proteins VP1 and VP4 (^∗) are generally used for phylogenetic analysis. RdRP, RNA-dependent RNA polymerase; UTR, untranslated region. (B) An icosahedral virion structure of HRV with a pentamer structure shown highlighting the external capsid proteins (VP1, VP2, and VP3) organization. VP1 is responsible for receptor engagement and VP4 is located beneath each monomeric unit and is responsible for genomic association with VPg. (C) Three distinct species of human rhinovirus have been identified (HRV-A, HRV-B, and HRV-C). The approximate number of types within each species classification and known receptors of each are shown.