Efficacy of recombinant measles virus expressing highly pathogenic avian influenza virus (HPAIV) antigen against HPAIV infection in monkeys

Tomoko Fujiyuki,Miho Hoshi,Shosaku Hattori,Hiroshi Kida,Fumihiko Yasui,Fusako Ikeda,Hiroki Sato,Yuri Kiso,Takeshi Kuraishi,Hyun-Jeong Kwon,Michinori Kohara,Misako Yoneda,Ryo Horie,Keisuke Munekata,Chieko Kai,Mio Omi

doi:10.1038/s41598-017-08326-x

Abstract

Highly pathogenic avian influenza virus (HPAIV) is a serious threat not only to domestic fowls but also to humans. Vaccines inducing long-lasting immunity against HPAIV are required. In the present study, we generated recombinant measles virus (MV) expressing the hemagglutinin protein of HPAIV without the multibasic site necessary for its pathogenicity in chickens using the backbone of an MV vaccine strain (rMV-Ed-H5HA) or a wild-type MV-derived mutant (rMV-HL-Vko-H5HA). We examined protective efficacy of the candidate vaccines in the monkey infection model by the challenge with a HPAIV (H5N1). Cynomolgus monkeys inoculated with the candidate vaccines produced both anti-H5 HA and anti-MV antibodies. They recovered earlier from influenza symptoms than unvaccinated monkeys after the challenge with the HPAIV strain. Chest radiography and histopathological analyses confirmed less severe pneumonia in the vaccinated monkeys. Vaccination tended to suppress viral shedding and reduced the interleukin-6 levels in the lungs. Furthermore, the vaccination with rMV-Ed-H5HA of monkeys with pre-existing anti-MV immunity induced the production of anti-H5 HA antibodies. These results suggest that both candidate vaccines effectively reduce disease severity in naïve hosts, and that rMV-Ed-H5HA is a particularly good candidate vaccine against HPAIV infection.

Highlights

Pathogenic avian influenza virus (HPAIV) is a serious threat to domestic fowls and to humans
These results suggest that both candidate vaccines effectively reduce disease severity in naïve hosts, and that recombinant MV (rMV)-Ed-H5HA is a good candidate vaccine against Highly pathogenic avian influenza virus (HPAIV) infection
HEK 293 cells were transfected with the resultant plasmid and supporting plasmids and overlain with B95a cells, and the recombinant viruses were rescued

Summary

Introduction

Pathogenic avian influenza virus (HPAIV) is a serious threat to domestic fowls and to humans. Vaccines inducing long-lasting immunity against HPAIV are required. Cynomolgus monkeys inoculated with the candidate vaccines produced both anti-H5 HA and anti-MV antibodies. They recovered earlier from influenza symptoms than unvaccinated monkeys after the challenge with the HPAIV strain. The vaccination with rMV-Ed-H5HA of monkeys with pre-existing anti-MV immunity induced the production of anti-H5 HA antibodies. These results suggest that both candidate vaccines effectively reduce disease severity in naïve hosts, and that rMV-Ed-H5HA is a good candidate vaccine against HPAIV infection. Utilization of the measles virus (MV) vector has been proposed to develop live vaccines for infectious diseases[7,8,9,10]. We expect that bivalent vaccine based on MV vaccine vector is useful to develop new vaccines against various emerging infectious diseases

Methods

Results

Conclusion