The potential of a universal influenza virus-like particle vaccine expressing a chimeric cytokine

Author:

Nerome Kuniaki1ORCID,Imagawa Toshifumi12ORCID,Sugita Shigeo3ORCID,Arasaki Youta1,Maegawa Kenichi1,Kawasaki Kazunori4,Tanaka Tsuyoshi5,Watanabe Shinji6,Nishimura Hidekazu7,Suzuki Tetsuro2,Kuroda Kazumichi8,Kosugi Isao9,Kajiura Zenta10

Affiliation:

1. Nerome Institute of Biological Resources, Nago, Japan

2. Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan

3. Equine Research Institute, Japan Racing Association, Shimotsuke, Japan

4. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Osaka, Japan

5. TORAY Industries, Inc., Iyo, Japan

6. Research Center for Influenza and Respiratory Viruses, National Institute of Infectious Diseases, Tokyo, Japan

7. Virus Research Center, Clinical Research Division, Sendai Medical Center, National Hospital Organization, Sendai, Japan

8. Division of Gastroenterology and Hepatology, Nihon University School of Medicine, Tokyo, Japan

9. Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

10. Division of Applied Biology, Facility of Textile Science and Technology, Shinshu University, Ueda, Japan

Abstract

The efficacy of the current influenza vaccines is frequently reduced because of antigenic drift, a trade-off of developing improved vaccines with broad cross-protective activity against influenza A viruses. In this study, we have successfully constructed a chimeric cytokine (CC) comprising the M2 protein, influenza A neuraminidase stalk, and interleukin-12. We produced virus-like particles (VLPs) containing CC and influenza hemagglutinin (HA) proteins using a baculovirus system in Eri silkworm pupae. The protective efficacy of the CCHA-VLP vaccine was evaluated in mice. The CCFkH5HA-VLP vaccine increased the survival rates of BALB/c mice, infected with a lethal dose of PRH1 and HKH5 viruses, to 80% and 100%, respectively. The results suggested that CCHA-VLP successfully induced potent cross-reactive protective immunity against infection with homologous and heterologous subtypes of the influenza A virus. This is the first study to design a CC-containing HA-VLP vaccine and validate its protective efficacy.

Funder

Shinshu University

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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