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

• Type of Material: Article
• Authors: Yu-Na Lee, Georgia State University; Hye Suk Hwang, Georgia State University; Min-Chul Kim, Georgia State University; Young-Tae Lee, Georgia State University; Yu-Jin Kim, Georgia State University; Frances Lee, Emory University; Sang-Moo Kang, Georgia State University
• Language: English
• Date: 2016-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nano.2015.11.007
• Title of Journal or Parent Work: Nanomedicine: Nanotechnology, Biology and Medicine
• ISSN: 1549-9634
• Volume: 12
• Issue: 3
• Start Page: 759
• End Page: 770
• Grant/Funding Information: 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: RSV; ANTIBODY; COTTON RATS; T-CELLS; Medicine, Research & Experimental; VACCINE; CONFERS PROTECTION; Science & Technology; IN-VIVO; BALB/C MICE; Neutralizing epitope vaccine; Life Sciences & Biomedicine; Viral vector; Research & Experimental Medicine; Respiratory syncytial virus; Science & Technology - Other Topics; Recombinant; Influenza virus; A VIRUS; DISEASE; F protein; Nanoscience & Nanotechnology
• Research Categories: Health Sciences, Immunology; Biology, Virology

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.