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Author Notes:

To whom correspondence should be addressed. Sang-Moo Kang, PhD, Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA, skang24@gsu.edu (S.M.K.), Telephone: 404 – 413-3588.

All authors declare no conflicts of interest.

Subjects:

Research Funding:

This work was supported by NIH/NIAID grants AI105170 (S.M.K.), AI119366 (S.M.K.), and AI093772 (S.M.K.).

The following reagent was obtained through BEI Resources, NIAID, NIH: Soluble Fusion Glycoprotein with C-Terminal Histidine Tag from Respiratory Syncytial Virus, A2, Recombinant Produced in 293F Cells, NR-28908.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Nanoscience & Nanotechnology
  • Medicine, Research & Experimental
  • Science & Technology - Other Topics
  • Research & Experimental Medicine
  • Influenza virus
  • Respiratory syncytial virus
  • Recombinant
  • Viral vector
  • F protein
  • Neutralizing epitope vaccine
  • A VIRUS
  • CONFERS PROTECTION
  • COTTON RATS
  • BALB/C MICE
  • T-CELLS
  • IN-VIVO
  • VACCINE
  • DISEASE
  • RSV
  • ANTIBODY

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

Tools:

Journal Title:

Nanomedicine: Nanotechnology, Biology and Medicine

Volume:

Volume 12, Number 3

Publisher:

, Pages 759-770

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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