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

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. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLPmore » do not induce lung cellular infiltrates and Th2 cytokine.« less

Authors:
; ; ; ; ; ; ;  [1];  [1];  [2];  [1]; ;  [1];  [2];  [1];  [1]
  1. Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)
  2. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22581696
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 494; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIBODIES; COTTON; DNA; EOSINOPHILS; FORMALDEHYDE; GLYCOPROTEINS; INFLAMMATION; LUNGS; LYMPHOKINES; PLASMIDS; RATS; VACCINES; VIRAL DISEASES; VIRUSES

Citation Formats

Hwang, Hye Suk, Lee, Young-Tae, Kim, Ki-Hye, Park, Soojin, Kwon, Young-Man, Lee, Youri, Ko, Eun-Ju, Jung, Yu-Jin, Lee, Jong Seok, National Institute of Biological Resources, Incheon, Kim, Yu-Jin, Lee, Yu-Na, Kim, Min-Chul, Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo, Cho, Minkyoung, and Kang, Sang-Moo, E-mail: skang24@gsu.edu. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease. United States: N. p., 2016. Web. doi:10.1016/J.VIROL.2016.04.014.
Hwang, Hye Suk, Lee, Young-Tae, Kim, Ki-Hye, Park, Soojin, Kwon, Young-Man, Lee, Youri, Ko, Eun-Ju, Jung, Yu-Jin, Lee, Jong Seok, National Institute of Biological Resources, Incheon, Kim, Yu-Jin, Lee, Yu-Na, Kim, Min-Chul, Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo, Cho, Minkyoung, & Kang, Sang-Moo, E-mail: skang24@gsu.edu. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease. United States. doi:10.1016/J.VIROL.2016.04.014.
Hwang, Hye Suk, Lee, Young-Tae, Kim, Ki-Hye, Park, Soojin, Kwon, Young-Man, Lee, Youri, Ko, Eun-Ju, Jung, Yu-Jin, Lee, Jong Seok, National Institute of Biological Resources, Incheon, Kim, Yu-Jin, Lee, Yu-Na, Kim, Min-Chul, Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo, Cho, Minkyoung, and Kang, Sang-Moo, E-mail: skang24@gsu.edu. Fri . "Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease". United States. doi:10.1016/J.VIROL.2016.04.014.
@article{osti_22581696,
title = {Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease},
author = {Hwang, Hye Suk and Lee, Young-Tae and Kim, Ki-Hye and Park, Soojin and Kwon, Young-Man and Lee, Youri and Ko, Eun-Ju and Jung, Yu-Jin and Lee, Jong Seok and National Institute of Biological Resources, Incheon and Kim, Yu-Jin and Lee, Yu-Na and Kim, Min-Chul and Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo and Cho, Minkyoung and Kang, Sang-Moo, E-mail: skang24@gsu.edu},
abstractNote = {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. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.},
doi = {10.1016/J.VIROL.2016.04.014},
journal = {Virology},
number = ,
volume = 494,
place = {United States},
year = {Fri Jul 15 00:00:00 EDT 2016},
month = {Fri Jul 15 00:00:00 EDT 2016}
}