Proof of concept in non-human primates of the heterologous prime-boost strategy combining dengue-2 virus and recombinant proteins including domain III of the viral envelope protein
Abstract
Live attenuated viruses are the most advanced candidates against a dengue infection. They have been demonstrated to be immunogenic in preclinical and clinical studies. However, due to their replicative capacity, they require several doses to achieve the balanced immune response against the four serotypes. The use of a suitable combination using nonreplicative immunogens, without viral interference, can help to induce such a balanced response. This work dealt with the proof of concept of the heterologous prime-boost strategy combining in the same schedule in non-human primates of a live virus and the recombinant proteins containing the domain III of the viral envelope. These combinations may result in condensed immunization schedules for humans, thus reducing the number of doses with attenuated virus and the dose time spacing. In both studies, the humoral and cellular immune responses after the boost dose with each recombinant protein were evaluated. In the second study, additionally, the possibility of shortening the schedule was assessed, an advantage related with this prime-boost strategy. The boost effect was demonstrated by the neutralizing antibodies induced after recombinant protein immunizations. Additionally, it was confirmed that these neutralizing antibodies were long lasting, also the animals were able to mount a specific cellular immune response after the boost. This study won the Annual Award of the Academy of Sciences of Cuba in 2012.
