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Protection against respiratory syncytial virus by inactivated influenza virus carrying a fusion protein neutralizing epitope in a chimeric hemagglutinin.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lee, Yu-Na Hwang, Hye Suk Kim, Min-Chul Lee, Young-Tae Kim, Yu-Jin Lee, F. Eun-Hyung Kang, Sang-Moo
Description	Country affiliation: United States Author Affiliation: Lee YN ( Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.); Hwang HS ( Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.); Kim MC ( Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA); Lee YT ( Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.); Kim YJ ( Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.); Lee FE ( Department of Medicine, Emory University, Atlanta, GA, USA.); Kang SM ( Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Electronic address: skang24@gsu.edu.)
Abstract	UNLABELLED: A desirable vaccine against respiratory syncytial virus (RSV) should induce neutralizing antibodies without eliciting abnormal T cell responses to avoid vaccine-enhanced pathology. In an approach to deliver RSV neutralizing epitopes without RSV-specific T cell antigens, we genetically engineered chimeric influenza virus expressing RSV F262-276 neutralizing epitopes in the globular head domain as a chimeric hemagglutinin (HA) protein. Immunization of mice with formalin-inactivated recombinant chimeric influenza/RSV F262-276 was able to induce RSV protective neutralizing antibodies and lower lung viral loads after challenge. Formalin-inactivated RSV immune mice showed high levels of pulmonary inflammatory cytokines, macrophages, IL-4-producing T cells, and extensive histopathology. However, RSV-specific T cell responses and enhancement of pulmonary histopathology were not observed after RSV infection of inactivated chimeric influenza/RSV F262-276. This study provides evidence that an inactivated vaccine platform of chimeric influenza/RSV virus can be developed into a safe RSV vaccine candidate without priming RSV-specific T cells and immunopathology. FROM THE CLINICAL EDITOR: Respiratory syncytial virus (RSV) is a major cause of respiratory tract illness and morbidity in children. Hence, there is a need to develop an effective vaccine against this virus. In this article, the authors engineered chimeric influenza virus to express RSV neutralizing epitopes. The positive findings in in-vivo experiments provide a beginning for future clinical trials and perhaps eventual product realization.
File Format	HTM / HTML
ISSN	15499634
Issue Number	3
Journal	Nanomedicine: Nanotechnology, Biology and Medicine
Volume Number	12
e-ISSN	15499642
Language	English
Publisher	Elsevier
Publisher Date	2016-04-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Nanotechnology Discipline Biotechnology
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Medicine Molecular Medicine Bioengineering Biomedical Engineering Pharmaceutical Science

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