RSV is worldwide the leading cause of serious airway infections. Up to 90% of children will be infected by the age of 2.

The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains and to be efficacious in preventing RSV-associated lower respiratory tract diseases in older adults. Although RSV F is highly conserved, variation does exist between strains. Here, we characterized variations in the major viral antigenic sites among contemporary RSV sequences when compared with RSVPreF3 and showed that, in older adults, RSVPreF3-AS01 broadly boosts neutralization responses against currently dominant and antigenically distant RSV strains. RSV-neutralizing responses are thought to play a central role in preventing RSV infection. Therefore, the breadth of RSVPreF3-AS01–elicited neutralization responses may contribute to vaccine efficacy against contemporary RSV strains and those that may emerge in the future.

Respiratory Syncytial Virus (RSV) poses a significant global health concern as a major cause of lower respiratory tract infections (LRTIs). Over the last few years, substantial efforts have been directed towards developing vaccines and therapeutics to combat RSV, leading to a diverse landscape of vaccine candidates. Notably, two vaccines targeting the elderly and the first maternal vaccine have recently been approved. The majority of the vaccines and vaccine candidates rely solely on a prefusion-stabilized conformation known for its highly neutralizing epitopes. Although, so far, this antigen design appears to be successful for the elderly, our current understanding remains incomplete, requiring further improvement and refinement in this field. Pediatric vaccines still have a long journey ahead, and we must ensure that vaccines currently entering the market do not lose efficacy due to the emergence of mutations in RSV’s circulating strains. This review will provide an overview of the current status of vaccine designs and what to focus on in the future. Further research into antigen design is essential, including the exploration of the potential of alternative RSV proteins to address these challenges and pave the way for the development of novel and effective vaccines, especially in the pediatric population.

Respiratory Syncytial Virus (RSV) is a very important viral pathogen in children, immunocompromised and cardiopulmonary diseased patients and the elderly. Most of the published research with RSV was performed on RSV Long and RSV A2, isolated in 1956 and 1961, yet recent RSV isolates differ from these prototype strains. Additionally, these viruses have been serially passaged in cell culture, which may result in adaptations that affect virus–host interactions. We have isolated RSV from mucosal secretions of 12 patients in the winters 2016–2017 and 2017–2018, of which eight RSV-A subtypes and four RSV-B subtypes. Passage 3 of the isolates was assessed for viral replication kinetics and infectious virus production in HEp-2, A549 and BEAS-2B cells, thermal stability at 37 °C, 32 °C and 4 °C, syncytia formation, neutralization by palivizumab and mucin mRNA expression in infected A549 cells. We observed that viruses isolated in one RSV season show differences on the tested assays. Furthermore, comparison with RSV A2 and RSV B1 reveals for some RSV isolates differences in viral replication kinetics, thermal stability and fusion capacity. Major differences are, however, not observed and differences between the recent isolates and reference strains is, overall, similar to the observed variation in between the recent isolates. One clinical isolate (BE/ANT-A11/17) replicated very efficiently in all cell lines, and remarkably, even better than RSV A2 in the HEp-2 cell line.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5–6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions. Prior research from our group showed that removing the N-glycan at position 116 (N116) in p27 led to higher neutralizing antibody responses and better protection against RSV. In this study, the effect of single, double and triple N-glycan deletion mutations in F p27 was evaluated. Surprisingly, all mutants exhibited similar expressions and functionality to the wild-type F protein. All F p27 glycomutants induced neutralizing antibodies and lowered lung viral loads after an RSV challenge in a mouse model. Although N-glycans in p27 influence immune responses, their exact role in RSV biology remains unclear. Possibly, these glycans, which are mostly conserved, play a role in other aspects of virus replication and biology.

Respiratory syncytial virus (RSV) remains a major global health issue. Therapeutic options are limited, but new prophylactics, all targeting the fusion (F) glycoprotein, were recently licensed. Although F sequence variation is limited, it is unclear if and how this variability translates to phenotypical differences. We analyzed full F sequences of 105 contemporary RSV isolates, gathered from children presenting with acute lower respiratory tract infections. Based on F antigenic site variation, 20 isolates were selected for functional characterization. Although RSV F diversity is generally low, the overall mean pairwise distance between RSV-A strains is higher than RSV-B (0.014 vs 0.008, P < 0.001). Sequence variability in the known monoclonal antibody (mAb)-binding sites seems insufficient to explain the divergent and often subgroup-dependent sensitivity to mAb neutralization. Despite comparable growth rates, mean syncytium size was higher (mean 61.68 [SD 24.51] vs 31.72 [SD 11.64], P < 0.001), and mean syncytium frequency was lower (mean 25.37 [SD 9.20] vs 47.85 [11.52], P < 0.001) in RSV-A strains. For all isolates, higher temperatures were associated with increased inactivation, although some RSV-A isolates displayed manifestly higher stability. Genomic and phenotypic variability among our contemporary RSV isolates was limited, with noticeable exceptions. The availability of new prophylactics targeting RSV F corroborates the importance of continued RSV surveillance to identify changes in the F sequence, including mutations that reduce mAb efficacy or lead to escape mutants. Surveillance should include both sequencing data and an evaluation of sensitivity to prophylactic antibodies, using contemporary clinical isolates. IMPORTANCE: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in young children worldwide. Recent progress has led to new ways to prevent serious RSV-associated disease. The virus’s fusion (F) protein is a key focus for vaccine development because it helps the virus enter host cells and is well conserved across different virus strains. However, it is unclear if small differences in the F protein sequence could affect how the virus behaves in vitro . In this study, we, therefore, analyzed 105 RSV samples from children under two who presented with respiratory infections. We selected 20 samples (12 RSV-A and 8 RSV-B) for functional testing, based on their F protein sequences. Phenotypic differences between clinical isolates and reference strains, such as virus stability at 4°C and susceptibility to monoclonal antibody neutralization, highlight the importance of using viruses isolated from recent clinical samples. Although significant functional differences were observed in traits related to the F protein, both between the RSV subgroups and within, the underlying molecular mechanisms remain unclear. Ongoing monitoring of RSV is critical to ensure current and future vaccines remain effective.