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

• Published in: Nanomedicine 2016-04, Vol.12 (3), p.759-770
• Main Authors: Lee, Yu-Na, DVM, PhD, Hwang, Hye Suk, MS, Kim, Min-Chul, DVM, PhD, Lee, Young-Tae, PhD, Kim, Yu-Jin, MS, Lee, Frances Eun-Hyung, MD, PhD, Kang, Sang-Moo, PhD
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neutralizing - immunology; Cell Line; Epitopes - genetics; Epitopes - immunology; Epitopes - therapeutic use; F protein; Female; Genetic Engineering - methods; Hemagglutinins, Viral - genetics; Hemagglutinins, Viral - immunology; Hemagglutinins, Viral - therapeutic use; Humans; Immunization; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza Vaccines - therapeutic use; Influenza virus; Internal Medicine; Mice; Mice, Inbred BALB C; Neutralizing epitope vaccine; Orthomyxoviridae - genetics; Orthomyxoviridae - immunology; Recombinant; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - genetics; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus Vaccines - therapeutic use; Respiratory Syncytial Viruses - genetics; Respiratory Syncytial Viruses - immunology; Viral vector
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2015.11.007

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 F 262 -276 neutralizing epitopes in the globular head domain as a chimeric hemagglutinin (HA) protein. Immunization of mice with formalin-inactivated recombinant chimeric influenza/RSV F 262 -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 F 262 -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.