Clinical and biological consequences of respiratory syncytial virus genetic diversity

Abstract

Respiratory syncytial virus (RSV) is one of the most common etiological agents of global acute respiratory tract infections with a disproportionate burden among infants, individuals over the age of 65, and immunocompromised populations. The two major subtypes of RSV (A and B) co-circulate with a predominance of either group during different epidemic seasons, with frequently emerging genotypes due to RSV’s high genetic variability. Global surveillance systems have improved our understanding of seasonality, disease burden, and genomic evolution of RSV through genotyping by sequencing of attachment (G) glycoprotein. However, the integration of these systems into international infrastructures is in its infancy, resulting in a relatively low number (~2200) of publicly available RSV genomes. These limitations in surveillance hinder our ability to contextualize RSV evolution past current canonical attachment glycoprotein (G)-oriented understanding, thus resulting in gaps in understanding of how genetic diversity can play a role in clinical outcome, therapeutic efficacy, and the host immune response. Furthermore, utilizing emerging RSV genotype information from surveillance and testing the impact of viral evolution using molecular techniques allows us to establish causation between the clinical and biological consequences of arising genotypes, which subsequently aids in informed vaccine design and future vaccination strategy. In this review, we aim to discuss the findings from current molecular surveillance efforts and the gaps in knowledge surrounding the consequence of RSV genetic diversity on disease severity, therapeutic efficacy, and RSV–host interactions.

RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models

“…Deep sequencing approaches subsequently helped to broader define RSV diversity, although still only a relatively limited number of sequence data is publicly available. Up to now, 37 genotypes have been identified for RSV B and 13 for RSV A, mainly based on genetic variation in the G glycoprotein (reviewed in [ 25 ]). It was reported that the evolutionary rate for both subtypes differs from each other, with a lower rate of nucleotide substitutions/site/year for RSV A than RSV B [ 26 ].…”

Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses

“…Although rapid evolution of antigenically variable mucosal viruses like influenza A viruses 35 and SARS-CoV-2 complicate next-generation vaccine design, other mucosal-only respiratory viruses, such as RSV, have shown much less antigenic plasticity 36 , 37 , 38 ; however, it still causes repeated infections over a lifetime without the development of long-term protective immunity. 39 , 40 Thus, although genetic and antigenic variability of viruses like influenza and SARS-CoV-2 make vaccine design more challenging, these factors by themselves cannot fully explain the lack of elicitation of long-term protective immunity against other respiratory mucosal viruses like the more phenotypically stable RSV.…”

Respiratory Syncytial Virus Infection: Treatments and Clinical Management

“…This review revises our understanding of the general pathophysiological features of RSV infection and the experimental default lines that exist for therapeutic development against it [ 30 , 31 ]. Moreover, we mainly discuss different vaccination and therapeutic developments in the domain of RSV clinical management and the understanding of the lack of market approval for these tested drugs [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. After reading this article, the audience will be able to understand the gaps in the literature and clinical developments that need to be undertaken via integrated and collaborative clinical research efforts so that RSV and associated infections can be well managed in the next couple of years.…”