Abstract
A universal influenza candidate vaccine that targets multiple conserved influenza virus epitopes from hemagglutinin (HA), neuraminidase (NA) and matrix (M2e) proteins was combined with the potent Army liposomal adjuvant (ALFQ) to promote induction of broad immunity to seasonal and pandemic influenza strains. The unconjugated and CRM-conjugated composite peptides formulated with ALFQ were highly immunogenic and induced both humoral and cellular immune responses in mice. Broadly reactive serum antibodies were induced across various IgG isotypes. Mice immunized with the unconjugated composite peptide developed antibody responses earlier than mice immunized with conjugated peptides, and the IgG antibodies were broadly reactive and neutralizing across Groups 1 and 2 influenza viruses. Multi-epitope unconjugated influenza composite peptides formulated with ALFQ provide a novel strategy for the development of a universal influenza vaccine. These synthetic peptide vaccines avoid the pitfalls of egg-produced influenza vaccines and production can be scaled up rapidly and economically.
Highlights
Influenza is a major cause of respiratory infections around the world
We demonstrate that ALF containing QS21 (ALFQ) adjuvant improved the immunogenicity of both conjugated and unconjugated composite influenza peptides and promoted the induction
Pep11 + 5906) (HA, NA and M2e) formulated with ALFQ were immunogenic in mice at all 3 doses tested (Figure 2)
Summary
Influenza is a major cause of respiratory infections around the world. The global influenza disease burden has been estimated to approach up to 1 billion infections, 3–5 million cases of severe disease and 300,000–500,000 deaths annually [1]. Influenza pandemics occur at various times and cause varying levels of severity and death [2]. Antibodies to HA are generally considered the key mediators of influenza immunity, and inhibition of HA activity has been the primary measure of vaccine effectiveness. Point mutations causing HA antigenic drift is the primary reason for variable and limited effectiveness of the seasonal influenza vaccine. While point mutations in the NA can occur, antigenic drift is lower than for HA among influenza A viruses [3,4]
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