title: Nanoparticle vaccines encompassing the respiratory syncytial virus (RSV) G protein CX3C chemokine motif induce robust immunity protecting from challenge and disease.
abstract: Nanoparticle vaccines were produced using layer-by-layer fabrication and incorporating respiratory syncytial virus (RSV) G protein polypeptides comprising the CX3C chemokine motif. BALB/c mice immunized with G protein nanoparticle vaccines produced a neutralizing antibody response that inhibited RSV replication in the lungs following RSV challenge. ELISPOT analysis showed that G nanoparticle vaccinated mice had increased levels of RSV G protein-specific IL-4 and IFN-γ secreting cells compared to controls following RSV challenge. Remarkably, RSV challenge of G protein nanoparticle vaccinated mice resulted in increased RSV M2-specific IL-4 and IFN-γ secreting T cells, and increased M2-specific H-2Kd-tetramer positive CD8(+) T cells in the lungs compared to controls. Cell type analysis showed vaccination was not associated with increased pulmonary eosinophilia following RSV challenge. These results demonstrate that vaccination of mice with the RSV G protein nanoparticle vaccines induces a potent neutralizing antibody response, increased G protein- and M2-specific T cell responses, and a reduction in RSV disease pathogenesis.
authors.affiliation: Department of Infectious Disease, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jorquera
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Choi
authors.forename: Katie E
authors.initials: KE
authors.lastname: Oakley
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Powell
authors.forename: James G
authors.initials: JG
authors.lastname: Boyd
authors.forename: Naveen
authors.initials: N
authors.lastname: Palath
authors.forename: Lia M
authors.initials: LM
authors.lastname: Haynes
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Anderson
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D018893:Bronchoalveolar Lavage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D020523:Chemokines, CX3C / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology* / Q000627:therapeutic use; D012136:Respiratory Syncytial Viruses; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D020523:Chemokines, CX3C; D000939:Epitopes; C502275:G glycoprotein, Respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; D015847:Interleukin-4; D007371:Interferon-gamma
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