Immune Netw.  2019 Jun;19(3):e18. 10.4110/in.2019.19.e18.

Respiratory Syncytial Virus Fusion Protein-encoding DNA Vaccine Is Less Effective in Conferring Protection against Inflammatory Disease than a Virus-like Particle Platform

Affiliations
  • 1Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. skang24@gsu.edu
  • 2Department of Microbiology, Chonnam National University Medical School, Hwasun 58128, Korea.
  • 3Green Cross Cell Corp., Yongin 16924, Korea.
  • 4Komipharm Co., Ltd., Siheung 15094, Korea.
  • 5Animal and Plant Quarantine Agency, Gimcheon 39660, Korea.
  • 6Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul 02447, Korea.
  • 7Meissa Vaccines, South San Francisco, CA 94080, USA.

Abstract

Formalin-inactivated respiratory syncytial virus (RSV) vaccination causes vaccine-enhanced disease (VED) after RSV infection. It is considered that vaccine platforms enabling endogenous synthesis of RSV immunogens would induce favorable immune responses than non-replicating subunit vaccines in avoiding VED. Here, we investigated the immunogenicity, protection, and disease in mice after vaccination with RSV fusion protein (F) encoding plasmid DNA (F-DNA) or virus-like particles presenting RSV F (F-VLP). F-DNA vaccination induced CD8 T cells and RSV neutralizing Abs, whereas F-VLP elicited higher levels of IgG2a isotype and neutralizing Abs, and germinal center B cells, contributing to protection by controlling lung viral loads after RSV challenge. However, mice that were immunized with F-DNA displayed weight loss and pulmonary histopathology, and induced F specific CD8 T cell responses and recruitment of monocytes and plasmacytoid dendritic cells into the lungs. These innate immune parameters, RSV disease, and pulmonary histopathology were lower in mice that were immunized with F-VLP after challenge. This study provides important insight into developing effective and safe RSV vaccines.

Keyword

RSV; F-VLP; F-DNA; Vaccine enhanced disease

MeSH Terms

Animals
B-Lymphocytes
Dendritic Cells
DNA*
Germinal Center
Immunoglobulin G
Lung
Mice
Monocytes
Plasmids
Respiratory Syncytial Virus Vaccines
Respiratory Syncytial Viruses*
T-Lymphocytes
Vaccination
Vaccines, Subunit
Viral Load
Weight Loss
DNA
Immunoglobulin G
Respiratory Syncytial Virus Vaccines
Vaccines, Subunit
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