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

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• 作者：Yu-Na Lee ; DVM ; PhD^a ; Hye Suk Hwang ; MS^a ; Min-Chul Kim ; DVM ; PhD^a ; ^b ; Young-Tae Lee ; PhD^a ; Yu-Jin Kim ; MS^a ; F. Eun-Hyung Lee ; MD ; PhD^c ; Sang-Moo Kang ; PhD^a ; ^{skang24@gsu.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Influenza virus ; Respiratory syncytial virus ; Recombinant ; Viral vector ; F protein ; Neutralizing epitope vaccine
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：12
• 期：3
• 页码：759-770
• 全文大小：1802 K

文摘

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.

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.