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- Title
Immunogenicity and protective efficacy of RSV G central conserved domain vaccine with a prefusion nanoparticle.
- Authors
Rainho-Tomko, Jennifer N.; Pavot, Vincent; Kishko, Michael; Swanson, Kurt; Edwards, Darin; Yoon, Heesik; Lanza, Lilibeth; Alamares-Sapuay, Judith; Osei-Bonsu, Robert; Mundle, Sophia T.; Murison, Dave A.; Gallichan, Scott; Delagrave, Simon; Wei, Chih-Jen; Zhang, Linong; Nabel, Gary J.
- Abstract
Respiratory syncytial virus (RSV) G glycoprotein has recently reemerged as a vaccine antigen due to its ability to elicit potent neutralizing antibodies and ameliorate disease in animal models. Here we designed three constructs to display the G central conserved domain (Gcc) focused on inducing broad and potent neutralizing antibodies. One construct displaying Gcc from both RSV subgroups trimerized via a C-terminal foldon (Gcc-Foldon) was highly immunogenic in mice and in MIMIC, a pre-immune human in vitro model. To explore an optimal RSV vaccine, we combined the Gcc-Foldon antigen with a stabilized pre-fusion-F nanoparticle (pre-F-NP) as a bivalent vaccine and detected no antigenic interference between the two antigens in the MIMIC model. In RSV-primed macaques, the bivalent vaccine elicited potent humoral responses. Furthermore, both Gcc-Foldon and the bivalent vaccine conferred effective protection against RSV challenge in mice. This two-component vaccine could potentially provide effective protection against RSV infection in humans and warrants further clinical evaluation.
- Subjects
MACAQUES; RESPIRATORY syncytial virus; IMMUNE response; VACCINE effectiveness; VACCINES
- Publication
NPJ Vaccines, 2022, Vol 7, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-022-00487-9