Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

Hye Suk Hwang; Young-Tae Lee; Ki-Hye Kim; Soojin Park; Young-Man Kwon; Youri Lee; Eun-Ju Ko; Yu-Jin Jung; Jong Seok Lee; Yu-Jin Kim; Yu-Na Lee; Min-Chul Kim; Minkyoung Cho; Sang-Moo Kang

doi:10.1016/j.virol.2016.04.014

Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

Virology. 2016 Jul:494:215-24. doi: 10.1016/j.virol.2016.04.014. Epub 2016 Apr 26.

Authors

Affiliations

¹ Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
² Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA; National Institute of Biological Resources, Incheon, South Korea.
³ Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA; Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo, Republic of Korea.
⁴ Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA. Electronic address: skang24@gsu.edu.

PMID: 27123586
DOI: 10.1016/j.virol.2016.04.014

Abstract

A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate.

Keywords: Cotton rats; Protection; Respiratory syncytial virus; Safety; Virus-like particle.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
Cytokines / metabolism
Disease Models, Animal
Immunization
Immunoglobulin G / immunology
Rats
Respiratory Syncytial Virus Infections / immunology*
Respiratory Syncytial Virus Infections / pathology
Respiratory Syncytial Virus Infections / prevention & control*
Respiratory Syncytial Virus Infections / virology
Respiratory Syncytial Virus Vaccines / administration & dosage
Respiratory Syncytial Virus Vaccines / adverse effects
Respiratory Syncytial Virus Vaccines / genetics
Respiratory Syncytial Virus Vaccines / immunology*
Respiratory Syncytial Viruses / genetics*
Respiratory Syncytial Viruses / immunology*
Sigmodontinae
Vaccines, DNA / administration & dosage
Vaccines, DNA / adverse effects
Vaccines, DNA / genetics
Vaccines, DNA / immunology*
Vaccines, Virus-Like Particle / administration & dosage
Vaccines, Virus-Like Particle / adverse effects
Vaccines, Virus-Like Particle / genetics
Vaccines, Virus-Like Particle / immunology*
Viral Envelope Proteins / genetics
Viral Envelope Proteins / immunology
Viral Fusion Proteins / genetics
Viral Fusion Proteins / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Cytokines
Immunoglobulin G
Respiratory Syncytial Virus Vaccines
Vaccines, DNA
Vaccines, Virus-Like Particle
Viral Envelope Proteins
Viral Fusion Proteins