Respiratory syncytial virus type B (RSV-B) is a highly contagious pathogen primarily transmitted through respiratory droplets, direct contact with infected individuals, or contaminated surfaces. The virus enters the host through the eyes, nose, or mouth and attacks the respiratory epithelial cells. RSV-B is a major cause of lower respiratory tract infections (LRTIs), particularly in infants, the elderly, and immunocompromised individuals, often leading to bronchiolitis or pneumonia. Its pathogenesis involves viral replication in respiratory epithelial cells, triggering an exaggerated immune response characterized by neutrophil infiltration, cytokine release (such as IL-6 and TNF-α), and excessive mucus secretion. This inflammatory cascade leads to airway obstruction and tissue damage. RSV-B peaks seasonally in temperate regions, typically in winter, where recurrent infection can occur due to incomplete immunity.
RSV-B belongs to the Pneumoviridae family and has a pleomorphic envelope approximately 150-250 nanometers in diameter. Its lipid bilayer is covered with three surface glycoproteins: attachment glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH). The G protein mediates host cell binding, while the F protein facilitates viral entry by inducing membrane fusion. The RSV-B genome consists of a single-stranded negative-sense RNA (approximately 15.2 kb) encoding 11 proteins, including the nucleocapsid (N), phosphoprotein β, matrix protein (M), and RNA-dependent RNA polymerase (L). Unlike RSV-A, RSV-B exhibits genetic variation in the G protein (particularly its hypervariable region), which influences antigenic diversity and immune evasion. Its genome is tightly associated with the N protein, forming a ribonucleoprotein (RNP) complex that is essential for viral replication. Nonstructural proteins (NS1 and NS2) modulate the host interferon response and enhance viral persistence.
Since RSV fusion protein (F) is more conserved than glycoprotein (G) among RSV strains and serotypes, most candidate vaccines target viral fusion protein (F) rather than glycoprotein to induce a broader range of protective neutralizing antibodies. Here, researchers screened two chemically modified mRNA vaccines expressing RSV prefusion stabilizer protein (preF) targeting RSV A2 and B subtypes, respectively. Antigen-specific binding antibodies, neutralizing antibodies, and T cell-mediated immune responses were evaluated after immunization. The results showed that the mRNA candidate vaccine induced strong antigen-specific binding antibodies, neutralizing antibody responses, and Th1-biased T cell responses in both mice and cotton rats. In addition, cotton rats vaccinated with mRNA vaccines had significantly reduced lung pathology and infectious lung virus loads, and no vaccine-enhanced respiratory disease (VERD) occurred. Together, these results indicate that mRNA-based vaccines induce strong humoral and cellular immunity and provide excellent protection against RSV A2 and RSV B subtypes in rodents.
To further explore the immunogenicity of the vaccine in cotton rats, T2A-preF or IRES-preF mRNA vaccines (4 µg, 10 µg, or 25 µg) or FI-RSV were injected intramuscularly into cotton rats twice, 3 weeks apart. Each group of cotton rats was immunized intranasally once, with RSV A2 as a positive control and PBS as a negative control. Serum was collected at different time points after the second immunization, and the binding antibody titers against the prefusion F protein and the neutralizing antibody titers against RSV A2 or RSV B were tested by ELISA (Figure 1A). The results showed that all mRNA vaccines could induce increased levels of RSV F protein antibodies in serum and produce neutralizing antibody titers. Regardless of the dose, the antibody titers induced by the T2A-preF mRNA vaccine peaked on day 28 and decreased significantly on day 35, but were still higher than the antibody titers on day 21. The IRES-preF mRNA vaccine group also showed the same trend (Figure 1B). All mRNA vaccines induced significantly higher neutralizing antibody titers against RSV A2 or RSV B strains compared with FI-RSV, the naive, or RSV A2 groups. However, there was no dose dependence (Figure 1C). In addition, ELISpot results showed that IFN-γ secretion by spleen T lymphocytes in the 10 µg T2A-preF or 25 µg IRES-preF mRNA group was significantly higher than that in the naive or FI-RSV group, which was consistent with the observations in mice (Figure 1D). Together, these results indicate that RSV mRNA vaccines induced strong humoral and Th1-biased cellular immune responses in cotton rats.
Figure 1. Cotton rat immunogenicity. (Liu J, et al., 2025)