The tetravalent formulation of domain III‐capsid proteins recalls memory B‐ and T‐cell responses induced in monkeys by an experimental dengue virus infection

Tetra DIIIC is a vaccine candidate against dengue virus (DENV) composed by four chimeric proteins that fuse the domain III of the envelope protein of each virus to the corresponding capsid protein. Containing B‐ and T‐cell epitopes, these proteins form aggregates after the incubation with an immunostimulatory oligodeoxynucleotide, and their tetravalent formulation induces neutralizing antibodies and cellular immune response in mice and monkeys. Also, Tetra DIIIC protects mice after challenge with each DENV, and the monovalent formulation obtained from DENV‐2 protects monkeys upon homologous viral challenge. However, in the last years, new evidences have arisen regarding domain III of DENV envelope protein as irrelevant target for neutralizing antibodies in humans. Nevertheless, vaccination with domain III induces a neutralizing antibody response that confers protection against re‐infection. In addition, it has been demonstrated that the induction of a cellular immune response is essential to protect during the infection. This response can also avoid severe manifestations of dengue disease, associated to the antibody‐dependent enhancement of the infection. In this study, we observed that Tetra DIIIC was able to boost the antiviral and neutralizing antibody responses previously generated in monkeys during an experimental DENV infection, demonstrating that domain III is targeted by B cells during the viral infection. Additionally, Tetra DIIIC successfully boosted the cellular immune response generated by the viruses, probably against T‐cells epitopes in the capsid proteins. These results highlight the functionality of Tetra DIIIC as a vaccine candidate against DENV. Dengue: Vaccine boosts immune response in previously infected monkeys An experimental dengue vaccine boosts both the antibody‐ and cell‐mediated immune responses in monkeys previously infected with the virus. A team led by Lázaro Gil and Lisset Hermida from the Center for Genetic Engineering and Biotechnology in Havana, Cuba, exposed nine rhesus macaques to three strains of dengue. Eight months later, the researchers immunized the monkeys with Tetra DIIIC, a vaccine composed of recombinant proteins from each of the four strains of the virus that cause dengue, and saw an increase in the memory B and T immune cell responses. These results, combined with the team's previous finding that Tetra DIIIC can elicit strong anti‐dengue immunity in monkeys not previously exposed to the virus, build the case f