Abstract

The influenza virus is a serious threat to public health worldwide. A novel avian influenza A (H7N9) virus with a mortality rate of approximately 30% has been identified as an unusually dangerous virus for humans by the World Health Organization. Pathogenic H7N9 continue to represent a public health concern, and several candidate vaccines are currently in development. We generated candidate H7N9 vaccine strains using reverse genetics, consisting of hemagglutinin and neuraminidase genes derived from a human H7N9 virus and the remaining genes from the PR8 (A/PuertoRico/8/34 (H1N1)) virus. This H7N9 vaccine exhibited superior efficacy when combined with MF59 compared to other adjuvants. Immunized BALB/c mice were followed to determine the duration of the protective immune response. Antibody levels decreased to between one-half and one-eighth of the peak values four months after the final dose of the vaccine. Previously vaccinated mice received an A/Zhejiang/DTID-ZJU01/2013 H7N9 challenge six months post-vaccination, and all remained protected. We also verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. The humoral immune response and Th2 cytokine production following influenza challenge was potently induced in the animals that received the split vaccine. Therefore, the split H7N9 influenza vaccine with the MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge even after six months.

Highlights

  • IntroductionHuman influenza virus infections with the H7N9: avian influenza A (H7N9) strain were first reported in China in February 2013 [1], and there have been five subsequent waves of infection

  • Human influenza virus infections with the H7N9: avian influenza A (H7N9) strain were first reported in China in February 2013 [1], and there have been five subsequent waves of infection.total of 1486 laboratory-confirmed cases of human infection with avian influenza A (H7N9) viruses in China, including at least 540 deaths, had been reported to the World Health Organization (WHO) as of May 23, 2017 [2]

  • Two weeks after the first vaccination, the geometric mean titers (GMTs) of the hemagglutinin inhibition (HI) titers in the groups immunized with HA antigen (Groups 3 and 5) were all within the range of 10-80, while all microneutralization (MN) titers were below 1:40

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Summary

Introduction

Human influenza virus infections with the H7N9 strain were first reported in China in February 2013 [1], and there have been five subsequent waves of infection. Total of 1486 laboratory-confirmed cases of human infection with avian influenza A (H7N9) viruses in China, including at least 540 deaths, had been reported to the World Health Organization (WHO) as of May 23, 2017 [2]. Several H7 influenza vaccines in clinical development have limited protective efficacy due to the poor immunogenicity of the H7 hemagglutinin (HA) in humans [4,5,6]. To overcome this challenge, the addition of adjuvants has been used to enhance immune responses

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