Respiratory syncytial virus fusion glycoprotein F, nucleoprotein N, and transcription anti-termination protein M2-1 (RSV F/N/M2-1)

The target Respiratory syncytial virus fusion glycoprotein F, nucleoprotein N, and transcription anti-termination protein M2-1 is a multi-antigen complex used in the design of viral vector vaccines, most notably the chimpanzee adenovirus-vectored candidate ChAd155-RSV [27, 29]. The fusion (F) glycoprotein is a surface-exposed protein essential for viral entry and is the primary target for neutralizing antibodies [16, 33]. The nucleoprotein (N) and transcription anti-termination protein M2-1 are internal proteins that are highly conserved and serve as major targets for T-cell mediated immunity [27, 33]. By incorporating these three proteins, vaccines aim to elicit a balanced immune response that includes both potent neutralizing antibodies and a Th1-biased cellular response [27, 29]. This approach is intended to provide broad protection across RSV subtypes and to avoid the risk of vaccine-enhanced respiratory disease (ERD), which has historically hindered RSV vaccine development [27, 33]. While the F protein is also the target of licensed monoclonal antibodies like palivizumab and nirsevimab, the inclusion of N and M2-1 is specific to active immunization strategies seeking to provide durable and comprehensive protection [26, 30].

Other names

RSV F-N-M2-1ChAd155-RSV antigensRSV F, N, and M2-1 proteins

The target set is utilized in vaccines to induce a dual immune response: the F protein elicits neutralizing antibodies that block viral entry, while the N and M2-1 proteins stimulate Th1-biased T-cell responses to clear infected cells and prevent immune-enhanced pathology. Monoclonal antibodies targeting the F component specifically inhibit viral-host cell membrane fusion, while small molecules or siRNAs targeting the N component inhibit viral replication and assembly.