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

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

10.4161/hv.28400

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This work was supported by the US Public Service research grant AI072139 (M.Z.) from the National Institute of Allergy and Infectious Diseases and an internal fund from Texas Tech University Health Sciences Center Paul L. Foster School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to David Topham for providing MDCK cells, to Richard Webby for providing PR8 influenza viral plasmid system and mouse adapted H1N1(A/California/04/2009) influenza virus and A/FM/1/47(H1N1) influenza virus, and to the NIH/NIAID funded BEI Resources for supplying seasonal influenza vaccines and influenza A/HongKong/1/68 (H3N2) and A/Aichi/2/1968 (H3N2) strains.