Esquemas de inmunización complementaria basados en la combinación de una formulación tetravalente de proteínas recombinantes y virus vivos atenuados: estrategia vacunal contra el dengue

Introduction: Dengue is one of the most important emerging diseases transmitted by mosquitoes; only one vaccine has been approved and licensed in 20 countries against DENV. This vaccine cannot be administered to children younger than 9 years, due to the increased risk of hospitalization observed in this age group. For this reason, the development of new vaccine candidates and/or immunization strategies continue to be a priority to the World Health Organization and the scientific community. Objectives: This work describes the results in prime-boost immunization schedules combining two different vaccine candidates: recombinant proteins and live attenuated vaccines. Firstly, we evaluated the capacity of Tetra DIIIC vaccine candidate to boost a memory immune response generated in DENV-immune monkeys and as a second study, we also evaluated in monkeys the combination of Tetra DIIIC with the LATV vaccine developed by NIAID and licensed to the Vietnamese company Vabiotech under the codename TV005. Methods: Macaca mulatta non-human primates were used in the studies. The tetravalent vaccine candidate Tetra DIIIC consists of recombinant proteins DIIIC-1-DIIIC4, corresponding to the four dengue virus serotypes, in adjuvant aluminum oxide. Tetravalent formulation of attenuated live viruses TV005 by Vabiotech included the virus strains DENV-1 Nauru/74 (WP), DENV-2 Tonga/74, DENV-3 Sleman/78, and DENV-4 Dominica/81. Results: Our results demonstrate that administration of Tetra DIIIC eight months after the infection was able to recall DENV specific memory B- and T-cell response. In addition, we demonstrate that animals primed with Tetra DIIIC (one or two doses) and later immunized with TV005 develop a neutralizing, protective antibody response against the four DENV serotypes, and that the immune response generated by Tetra DIIIC reduces LATV viremia significantly, which might reduce the reactogenicity that has afflicted the latter during clinical trials. Results described here highlight the possibility to combine our vaccine candidate Tetra DIIIC with live-attenuated tetravalent vaccine in a prime/boost strategy for immunizations. The present study supports the prime-boost strategies as alternative and promissory approaches solving the troubles associated with each individual antigen included in the combination.