Hemagglutinin-based DNA vaccines containing trimeric self-assembling nanoparticles confer protection against influenza

J Leukoc Biol. 2022 Sep;112(3):547-556. doi: 10.1002/JLB.6A1021-535R. Epub 2022 Jan 17.

Abstract

Influenza viruses continue to threaten public health, and currently available vaccines provide insufficient immunity against seasonal and pandemic influenza. The use of recombinant trimeric hemagglutinin (HA) as an Ag provides an attractive alternative to current influenza vaccines. Aiming to develop an effective vaccine with rapid production, robust immunogenicity, and high protective efficiency, a DNA vaccine was designed by fusing influenza virus HA with self-assembled ferritin nanoparticles, denoted as HA-F. This candidate vaccine was prepared and purified in a 293-6E cell eukaryotic expression system. After BALB/c mice were immunized with 100 μg of HA-F DNA 3 times, HA-F elicited significant HA-specific humoral immunity and T cell immune responses. The HA-F DNA vaccine also conferred protection in mice against a lethal infection of homologous A/17/California/2009/38 (H1N1) virus. These results suggest that the HA-F DNA vaccine is a competitive vaccine candidate and presents a promising vaccination approach against influenza viruses.

Keywords: cellular immunity; cytokine; humoral immunity; immunogenicity; neutralizing Ab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinins
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles*
  • Orthomyxoviridae Infections*
  • Vaccines, DNA*

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Influenza Vaccines
  • Vaccines, DNA