Immunization of rhesus monkeys with a recombinant of modified vaccinia virus Ankara expressing a truncated envelope glycoprotein of dengue type 2 virus induced resistance to dengue type 2 virus challenge

Dengue epidemics increasingly pose a public health problem in most countrie s of the tropical and subtropical areas. Despite decades of research, devel opment of a safe and effective live dengue virus vaccine is still at the ex perimental stage. To explore an alternative vaccine strategy, we employed t he highly attenuated, replication-deficient modified vaccinia Ankara (MVA) as a vector to construct recombinants for expression of the major envelope glycoprotein of one or more dengue virus serotypes. MVA recombinants expres sing the highly immunogenic C-terminally truncated dengue type 2 virus (DEN 2) or dengue type 4 virus (DEN4) envelope protein (E), approx. 80% of the f ull-length, were evaluated for their protective immunity in animal models. Each of these recombinants elicited an elevated antibody response to DEN2 o r DEN4 E in mice following the booster inoculation, as detected by radio-im munoprecipitation. Recombinant MVA-DEN2 80%E, but not MVA-DEN4 80%E, induce d a neutralizing antibody response. The MVA-DEN2 80%E recombinant was chose n to further evaluate its ability to induce resistance to wild type DEN2 ch allenge in monkeys. Monkeys immunized twice with recombinant MVA-DEN2 80%E developed a low to moderate antibody response and were partially protected against DEN2 challenge, as determined by the viremia pattern. Importantly, the subsequent study showed that all four monkeys immunized with the recomb inant in a three dose schedule developed an increased level of antibodies a nd were completely protected against DEN2 challenge. The potential efficacy of recombinant MVA-DEN2 80%E to protect primates against dengue infection suggests that construction and evaluation of MVA recombinants expressing ot her serotypes of dengue virus E for use in a tetravalent vaccine strategy m ight be warranted. Published by Elsevier Science Ltd.