A dose-response study in mice of the vaccine preparation containing the diiic-2 protein aggregated with the oligodeoxinucleotide 39m

Abstract

The Cuban dengue vaccine program relies on the subunit vaccine based on two specific viral regions: the domain III of the envelope protein and the capsid protein. Previously, we reported the immunogenicity and protection capacity in mice and monkeys of the chimeric protein DIIIC-2, formed by the two described viral regions, highly aggregated with the ODN 39M and adjuvanted in alum. In the present work, different quantities of the ODN 39M were tested for their immunogenicity in mice. As a result, the formulation containing the protein aggregated with 2 µg of the ODN was the optimal condition in terms of cell-mediated immunity thereby; it was selected to be further studied. The second mice experiment was directed to study the effect of the formulation dose on their immunogenicity and protective capacity. Results revealed the best immunogenicity profile for the lowest quantity tested whereas the protection assay revealed an inverse behavior. Upon virus challenge, the group inducing the lowest immune response generated the best protection profile and only 40% of protection was obtained in the group generating the highest immunogenicity. Taken together we strongly recommend performing a dose study in non-human primates to find the optimal dose for inducing the best protective response

Keywords

• Dengue
• vaccine
• viruses
• immunogenicity
• experiment
• study