Chimeric Virus-like Particles Co-Displaying Hemagglutinin Stem and the C-Terminal Fragment of DnaK Confer Heterologous Influenza Protection in Mice

Viruses. 2022 Sep 23;14(10):2109. doi: 10.3390/v14102109.

Abstract

Influenza virus hemagglutinin (HA) stem is currently regarded as an extremely promising immunogen for designing universal influenza vaccines. The appropriate antigen-presenting vaccine vector would be conducive to increasing the immunogenicity of the HA stem antigen. In this study, we generated chimeric virus-like particles (cVLPs) co-displaying the truncated C-terminal of DnaK from Escherichia coli and H1 stem or full-length H1 antigen using the baculovirus expression system. Transmission electronic micrography revealed the expression and presentation of H1 stem antigens on the surface of VLPs. Vaccinations of mice with the H1 stem cVLPs induced H1-specific immune responses and provided heterologous immune protection in vivo, which was more effective than vaccinations with VLPs displaying H1 stem alone in protecting mice against weight loss as well as increasing survival rates after lethal influenza viral challenge. The results indicate that the incorporation of the truncated C-terminal of DnaK as an adjuvant protein into the cVLPs significantly enhances the H1-specific immunity and immune protection. We have explicitly identified the VLP platform as an effective way of expressing HA stem antigen and revealed that chimeric VLP is an vaccine vector for developing HA stem-based universal influenza vaccines.

Keywords: DnaK; hemagglutinin stem; influenza virus; universal vaccine; virus-like particle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinins
  • Humans
  • Influenza Vaccines* / genetics
  • Influenza, Human* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections* / prevention & control
  • Orthomyxoviridae*
  • Vaccines, Virus-Like Particle* / genetics

Substances

  • Influenza Vaccines
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Antibodies, Viral
  • Vaccines, Virus-Like Particle

Grants and funding

This research was supported by grants 31900670 and 81971566 from the National Natural Science Foundation of China, 2020JJ4176, and 2021SK2030 from the Natural Science Foundation of Hunan Province, Hunan Province Postdoctoral Program for Innovative Talent (2021RC2060), and Double-First Class Construction Funds of Hunan University (521119400156).