The RSVPreF3-AS01 vaccine elicits broad neutralization of contemporary and antigenically distant respiratory syncytial virus strains

Abstract

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.

All Eyes on the Prefusion-Stabilized F Construct, but Are We Missing the Potential of Alternative Targets for Respiratory Syncytial Virus Vaccine Design?

“…The construct is derived from the RSV A2 strain, the prototype RSV lab strain [ 94 , 95 ]. The antigen construct is based on the prefusion-stabilized structure of Prof. Dr. McLellan with the following mutations: the introduction of a disulfide bridge (S155C and S290C) and a hydrophobic cavity (S190F and V207L) [ 82 , 96 ]. This antigen construct was developed for elderly and maternal immunization.…”

Design and Preclinical Evaluation of a Nanoparticle Vaccine against Respiratory Syncytial Virus Based on the Attachment Protein G

“…These vaccines use the F protein stabilized in the prefusion conformation as a vaccine immunogen and are either based on RSV-A or a combination of RSV-A and RSV-B [ 13 , 14 ]. Although both vaccines have shown high efficacy against contemporary RSV-A and RSV-B strains, the F protein sequence is subject to drift mutations, possibly hampering preF-based vaccine efficacy in the future [ 41 ]. A solution would be to monitor the accumulation of mutations in the F protein and to update the preF-based RSV vaccines to match the circulating strains.…”

Respiratory syncytial virus immunoprophylaxis: Novel opportunities and a call for equity

“…45 Promisingly, a recent study also shows that immunization of elderly subjects with RSVPreF3 elicits neutralizing antibody responses not only against currently circulating RSV strains but also against antigenically distant ones, indicating that it may also confer protection if novel viral variants emerge without a need to update the vaccines, contrary to COVID-19 vaccinations. 47,48 The existing studies highlight that such a vaccine could help decrease the RSV burden among older populations in LMICs.…”