Nanoparticle Vaccines Encompassing the Respiratory Syncytial Virus (RSV) G Protein CX3C Chemokine Motif Induce Robust Immunity Protecting from Challenge and Disease

• Authors: Patricia A. Jorquera, University of Georgia; Youngjoo Choi, University of Georgia; Katie E. Oakley, University of Georgia; Thomas J. Powell, Artificial Cell Technologies; James G. Boyd, Artificial Cell Technologies; Naveen Palath, Artificial Cell Technologies; Lia M. Haynes, Centers for Disease Control and Prevention; Larry J Anderson, Emory University; Ralph A. Tripp, University of Georgia
• Journal Title: PLoS ONE
• Volume: Volume 8, Number 9
• Publisher: Public Library of Science | 2013-09-10, Pages e74905-e74905
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0074905
• Subjects: Biology, Virology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; ATTACHMENT G-GLYCOPROTEIN; T-CELL RESPONSES; G FUSION PROTEIN; BALB/C MICE; DENDRITIC CELLS; F-GLYCOPROTEIN; SEROPOSITIVE CHILDREN; ACID) NANOPARTICLES; ANTIBODY-RESPONSE; SUBUNIT VACCINE

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.