Protective antigenic sites identified in respiratory syncytial virus fusion protein reveals importance of p27 domain

• DOI: 10.15252/emmm.202013847
• Publication Date: 2021-11-09T07:50:18Z
• Authors: Jeehyun Lee; Youri Lee; Laura Klenow; Elizabeth M Coyle; Juanjie Tang; Supriya Ravichandran; Hana Golding; Surender Khurana
• Keywords: epitope; Medicine (General); Mice, Inbred BALB C; 0303 health sciences; F protein; RSV; Articles; Respiratory Syncytial Virus Infections; neutralization; QH426-470; Antibodies, Viral; Antibodies, Neutralizing; 3. Good health; Mice; 03 medical and health sciences; R5-920; vaccine; Respiratory Syncytial Virus, Human; Genetics; Respiratory Syncytial Virus Vaccines; Animals; Viral Fusion Proteins

Respiratory syncytial virus (RSV) vaccines primarily focused on surface fusion (F) protein are under development. Therefore, to identify RSV-F protective epitopes, we evaluated 14 antigenic sites recognized following primary human RSV infection. BALB/c mice were vaccinated with F peptides, F proteins, or RSV-A2, followed by rA2-Line19F challenge. F peptides generated binding antibodies with minimal in vitro neutralization titers. However, several F peptides (including Site II) reduced lung viral loads and lung pathology scores in animals, suggesting partial protection from RSV disease. Interestingly, animals vaccinated with peptides (aa 101-121 and 110-136) spanning the F-p27 sequence, which is only present in unprocessed F0 protein, showed control of viral loads with significantly reduced pathology compared with mock-vaccinated controls. Furthermore, we observed F-p27 expression on the surface of RSV-infected cells as well as lungs from RSV-infected mice. The anti-p27 antibodies demonstrated antibody-dependent cellular cytotoxicity (ADCC) of RSV-infected A549 cells. These findings suggest that p27-mediated immune response may play a role in control of RSV disease in vivo, and F-p27 should be considered for inclusion in an effective RSV vaccine.