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Antiviral Res. 2014 Nov;111:129-35. doi: 10.1016/j.antiviral.2014.09.005. Epub 2014 Sep 18.

Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins.

Author information

1
Department of Pediatrics, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA.
2
Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, Republic of Korea; Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
3
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
4
Department of Pathology, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
5
Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
6
Department of Pediatrics, Emory University, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA. Electronic address: martin.moore@emory.edu.

Abstract

Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in infants and a high priority for vaccine development. We previously reported that RSV virus-like particles (VLPs) expressing either the fusion (F) or attachment (G) glycoprotein could confer protection against RSV challenge in BALB/c mice. Here, we tested the hypothesis that RSV VLP vaccine efficacy can be enhanced by mixing RSV VLP F and RSV VLP G, and we analyzed host responses to these RSV VLPs. Mice were immunized with VLP F, VLP G, or VLP F+VLP G. Lung viral loads in BALB/c mice following RSV strain A2-line19F challenge were lower in mice vaccinated with RSV VLP F+VLP G compared to VLP F- or VLP G-vaccinated mice. Vaccination with VLP F or VLP F+VLP G induced similar levels of neutralizing antibodies. The enhanced protection against RSV challenge induced by vaccination with RSV VLP F+VLP G correlated with CD8 T cells producing T helper type 1 cytokines. VLP G vaccination alone followed by challenge resulted in immunopathology similar to formalin-inactivated RSV vaccination and RSV challenge. Taken together, mixed VLP F+VLP G provided a high level of protection against RSV without vaccine-induced immunopathology, but VLP G vaccination enhanced disease when used alone.

KEYWORDS:

Lung pathology; RSV attachment glyco (G) protein; RSV fusion (F) protein; Respiratory syncytial virus; Virus like particle (VLP)

PMID:
25239522
PMCID:
PMC4252885
DOI:
10.1016/j.antiviral.2014.09.005
[Indexed for MEDLINE]
Free PMC Article

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