HA1-2-fljB Vaccine Induces Immune Responses against Pandemic Swine-Origin H1N1 Influenza Virus in Mice

Abstract

In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of Salmonella typhimurium fljB. The recombinant HA1-2-fljB protein was expressed efficiently in Escherichia coli, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.