Open AccessProtective antigenic sites identified in respiratory syncytial virus fusion protein reveals importance of p27 domain
Author(s) -
Lee Jeehyun,
Lee Youri,
Klenow Laura,
Coyle Elizabeth M,
Tang Juanjie,
Ravichandran Supriya,
Golding Hana,
Khurana Surender
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202013847
Subject(s) - virology , epitope , virus , biology , antibody , antigen , fusion protein , immune system , antibody dependent cell mediated cytotoxicity , paramyxoviridae , neutralizing antibody , in vivo , immunology , viral disease , recombinant dna , monoclonal antibody , biochemistry , microbiology and biotechnology , gene
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.