The dengue envelope glycoprotein (E) is the major component of virion surface and its ectodomain is composed of domains I, II and III. This protein is the main target for the development of a dengue vaccine with induction of neutralizing antibodies. In the present work, we tested two different vaccination strategies, with combined immunizations in a prime/booster regimen or simultaneous inoculation with a DNA vaccine (pE1D2) and a chimeric yellow fever/dengue 2 virus (YF17D-D2). The pE1D2 DNA vaccine encodes the ectodomain of the envelope DENV2 protein fused to t-PA signal peptide, while the YF17D-D2 was constructed by replacing the prM and E genes from the 17D yellow fever vaccine virus by those from DENV2. Balb/c mice were inoculated with these two vaccines by different prime/booster or simultaneous immunization protocols and most of them induced a synergistic effect on the elicited immune response, mainly in neutralizing antibody production. Furthermore, combined immunization remarkably increased protection against a lethal dose of DENV2, when compared to each vaccine administered alone. Results also revealed that immunization with the DNA vaccine, regardless of the combination with the chimeric virus, induced a robust cell immune response, with production of IFN-γ by CD8+ T lymphocytes.
Introdução: O desenvolvimento de uma vacina tetravalente que confira imunidade protetora de longa duração contra os quatro sorotipos do vírus da dengue é uma das prioridades da OMS. Atualmente, algumas vacinas contra dengue estão em teste, entre elas, a vacina quimérica de vírus vivo atenuado que utiliza, como vetor viral, o vírus vacinal da febre amarela. A produção do vírus quimérico ocorre em células de origem animal e as diretrizes para produção de vacina de vírus vivo atenuado exigem que a concentração de DNA residual celular seja menor que 10 ng/dose. Para alcançar tal objetivo, é necessário que a suspensão viral passe por processos de clarificação e purificação.
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