Protective capacity of vaccine candidates against dengue virus type 2 based on the capsid protein and the oligodeoxynucleotide 39M

Vaccine formulations of the chimeric DIIIC-2 protein with different ODNs displaying adjuvant capacity were tested in mice against dengue virus serotype 2. DIIIC-2 comprises domain III from the envelope protein fused to the N-terminal region of the capsid protein. One of the ODNs, named ODN 39M, combines CpG motifs described as immunostimulatory active in mice, monkeys and human cells. The ODN sequence determined the immune response pattern generated, since ODN 39M was the only ODN inducing a Th1 response similar to that induced by the viral infection in mice. Hence, ODN 39M was aggregated with either the capsid protein of dengue-2 (C-2) or the DIIIC-2 protein, and both formulations were adjuvanted in alum. Upon administration in two mice models and in non-human primates, both formulations induced protection after the viral challenge. This was the first demonstration of the protective capacity induced by the vaccine formulation 39M-DIIIC-2 in non-human primates and in transgenic mouse models which develop dengue-like clinical symptoms. Moreover, viremia levels were reduced in non-human primates with the 39M-C-2 formulation. This was the first evidence ever on the induction of a functional immune response against dengue virus by vaccination in non-human primates, regardless the presence of neutralizing antibodies. Moreover, this was the first work describing protection in monkeys with a formulation that is suitable for human use and combines recombinant proteins from dengue virus with alum. This research granted the 2014 Award of the Cuban National Academy of Sciences.