Open AccessProtection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein
Author(s) -
Schepens Bert,
Sedeyn Koen,
Vande Ginste Liesbeth,
De Baets Sarah,
Schotsaert Michael,
Roose Kenny,
Houspie Lieselot,
Van Ranst Marc,
Gilbert Brian,
Rooijen Nico,
Fiers Walter,
Piedra Pedro,
Saelens Xavier
Publication year - 2014
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.201404005
Subject(s) - extracellular , mechanism of action , virology , mechanism (biology) , virus , chemistry , respiratory system , domain (mathematical analysis) , pneumovirinae , biology , microbiology and biotechnology , paramyxoviridae , biochemistry , viral disease , in vitro , mathematical analysis , philosophy , mathematics , epistemology , anatomy
Infections with human respiratory syncytial virus ( HRSV ) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain ( SH e) of the small hydrophobic ( SH ) protein of HRSV , reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of Fcγ RI and Fcγ RIII . Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SH e‐specific antibodies. HRSV ‐infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SH e‐based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SH e. Using SH e as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T‐cell responses could be complemented with a SH e‐based antigen to further improve immune protection.