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.
Copyright © 2016. Published by Elsevier Inc.
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