Abstract
BackgroundMultiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic. Therefore, new influenza vaccines to prevent the co-existence of multiple subtypes within a host and cross-species transmission of influenza are urgently needed.MethodsHere we report a multi-epitope DNA vaccine targeted towards multiple subtypes of the influenza virus. The protective hemagglutinin (HA) antigens from H5/H7/H9 subtypes were screened for MHC II class-restricted epitopes overlapping with predicted B cell epitopes. We then constructed a DNA plasmid vaccine, pV-H3-EHA-H1, based on HA antigens from human influenza H3/H1 subtypes combined with the H5/H7/H9 subtype Th/B epitope box.ResultsEpitope-specific IFN-γ ELISpot responses were significantly higher in the multi-epitope DNA group than in other vaccine and control groups (P < 0.05). The multi-epitope group significantly enhanced Th2 cell responses as determined by cytokine assays. The survival rate of mice given the multi-epitope vaccine was the highest among the vaccine groups, but it was not significantly different compared to those given single antigen expressing pV-H1HA1 vaccine and dual antigen expressing pV-H3-H1 vaccine (P > 0.05). No measurable virus titers were detected in the lungs of the multi-epitope immunized group. The unique multi-epitope DNA vaccine enhanced virus-specific antibody and cellular immunity as well as conferred complete protection against lethal challenge with A/New Caledonia/20/99 (H1N1) influenza strain in mice.ConclusionsThis approach may be a promising strategy for developing a universal influenza vaccine to prevent multiple subtypes of influenza virus and to induce long-term protective immune against cross-species transmission.
Highlights
Multiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic
We report here the generation and evaluation of the immunogenicity of a DNA vaccine expressing HA based on human influenza H3/H1 combined with a class II major histocompatibility complex (MHC) multi-epitope antigen
BCEPRED is an improved linear B cell epitope prediction method that utilizes multi-parameter analysis to predict potential B cell epitopes. Comprehensive analyses of both T helper (Th) and B cell epitopes were performed to obtain a set of epitopes in which the predicted Th epitopes would contain potential B cell epitopes
Summary
Multiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic. New influenza vaccines to prevent the co-existence of multiple subtypes within a host and cross-species transmission of influenza are urgently needed. It is important to develop new approaches towards preventing seasonal infections as well as potential pandemics of influenza. Based on their internal protein antigens, different influenza viruses can be divided into 3 types: A, B, or C. In recent years, multiple subtypes (H5/H7/H9) of the avian influenza virus (AIV) have been able to cross the species barrier to infect humans [3,4]. Due to the rapidly changing influenza virus or the phenomena of “antigenic shift” and “antigenic drift”, developing a vaccine that can protect against all possible circulating viruses is extremely challenging
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