title: Preclinical evaluation of bacterially produced RSV-G protein vaccine: Strong protection against RSV challenge in cotton rat model.
abstract: In current study, we evaluated the safety and protective efficacy of recombinant unglycosylated RSV G protein ectodomain produced in E. coli (in presence and absence of oil-in-water adjuvant) in a preclinical RSV susceptible cotton rat challenge model compared to formaldehyde inactivated RSV (FI-RSV) and live RSV experimental infection. The adjuvanted G protein vaccine induced robust neutralization antibody responses comparable to those generated by live RSV infection. Importantly, adjuvanted G protein significantly reduced viral loads in both the lungs and nose at early time points following viral challenge. Antibody kinetics determined by Surface Plasmon Resonance showed that adjuvanted G generated 10-fold higher G-binding antibodies compared to non-adjvuanted G vaccine and live RSV infection, which correlated strongly with both neutralization titers and viral load titers in the nose and lungs post-viral challenge. Antibody diversity analysis revealed immunodominant antigenic sites in the N- and C-termini of the RSV-G protein, that were boosted >10-fold by adjuvant and inversely correlated with viral load titers. Enhanced lung pathology was observed only in animals vaccinated with FI-RSV, but not in animals vaccinated with unadjuvanted or adjuvanted RSV-G vaccine after viral challenge. The bacterially produced unglycosylated G protein could be developed as a protective vaccine against RSV disease.
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20903, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fuentes
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20903, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Klenow
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20903, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD, 20903, USA.
authors.forename: Surender
authors.initials: S
authors.lastname: Khurana
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D009500:Neutralization Tests; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D016205:Sigmodontinae; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; C502275:G glycoprotein, Respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins