Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses

Hum Vaccin Immunother. 2014;10(5):1211-20. doi: 10.4161/hv.28407. Epub 2014 Mar 14.

Abstract

Frequent mutation of influenza viruses keep vaccinated and non-vaccinated populations vulnerable to new infections, causing serious burdens to public health and the economy. Vaccination with universal influenza vaccines would be the best way to effectively protect people from infection caused by mismatched or unforeseen influenza viruses. Presently, there is no FDA approved universal influenza vaccine. In this study, we expressed and purified a fusion protein comprising of influenza matrix 2 protein ectodomain peptides, a centralized influenza hemagglutinin stem region, and cholera toxin subunit B. Vaccination of BALB/c mice with this novel artificial antigen resulted in potent humoral immune responses, including induction of specific IgA and IgG, and broad protection against infection by multiple influenza viruses. Furthermore, our results demonstrated that when used as a mucosal antigen, cholera toxin subunit B improved antigen-stimulated T cell and memory B cell responses.

Keywords: broad spectrum vaccine; cholera toxin subunit B; influenza; intranasal vaccination; protective immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / administration & dosage*
  • Antigens, Viral / immunology*
  • Cholera Toxin / administration & dosage*
  • Cholera Toxin / genetics
  • Cholera Toxin / immunology*
  • Female
  • Immunization / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Molecular Sequence Data
  • Orthomyxoviridae / drug effects
  • Orthomyxoviridae / genetics
  • Orthomyxoviridae / immunology*

Substances

  • Antigens, Viral
  • Cholera Toxin