Creation of synthetic genes in order to increase the cross-reactivity and protective efficacy of Hantavirus DNA-vaccines

Annually, hantaviruses infect more than 150,000 people worldwide, resulting in thousands of deaths, why prophylactic treatment such as vaccination against human pathogens among the hantaviruses is highly desirable. The immunological cross-reactivity and high genetic conservation between these viruses could be one key towards a common vaccination strategy. In this study, we have initiated an investigation exploring the possibility of creating one "universal" DNA vaccine against several of the human pathogenic hantaviruses. We have constructed two synthetic genes, multi-epitope constructs, derived from proposed B- and T-cell epitopes of the S-genes from five different hantaviruses. The epitopes have been modified for increased cross-reactivity by individual amino acid substitutions towards common consensus sequences within the proposed epitope. Furthermore, the individual epitopes were flanketd with immuno-stimulatory DNA sequences (CpG) for enhanced immunogenicity. This report contains the initial results from the efforts of exploring the possibility of a multi-epitope vaccine with an enhanced cross-reactivity. The synthetic genes and the corresponding full-length S-genes were successfully expressed in bacterial for the production of antigens used to evaluate the immune response obtained in animal model systems. The genes were also expressed in eukaryotic cells, indicating the possibility of in vivo expression of the encoded antigens in vaccinated animals. Interestingly, the synthetic proteins turned out to be very stable, which is favorable for the generation of a strong and long-lasting immune response.