Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease.
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.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Hye Suk
HS
Hwang
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Young-Tae
YT
Lee
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Ki-Hye
KH
Kim
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Soojin
S
Park
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Young-Man
YM
Kwon
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Youri
Y
Lee
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Eun-Ju
EJ
Ko
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Yu-Jin
YJ
Jung
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.
Jong Seok
JS
Lee
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Yu-Jin
YJ
Kim
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.
Yu-Na
YN
Lee
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.
Min-Chul
MC
Kim
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA.
Minkyoung
M
Cho
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA, USA. Electronic address: skang24@gsu.edu.
Sang-Moo
SM
Kang
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics* / Q000276:immunology*; D016205:Sigmodontinae; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D022261:Respiratory Syncytial Virus Vaccines; D019444:Vaccines, DNA; D058425:Vaccines, Virus-Like Particle; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins
Cotton rats; Protection; Respiratory syncytial virus; Safety; Virus-like particle