Induction of protective immunity against Dengue virus type 2: comparison of candidate live attenuated and recombinant vaccines

Dengue (DEN) viruses (serotypes 1 to 4) are mosquito-borne flaviviruses whi ch cause about fifty million human infections annually and represent an exp anding public health problem in the tropics. At present, there are no safe and effective vaccines which induce protective immunity to all four serotyp es of DEN. Natural infection or vaccination with native and recombinant pro teins may induce an immune response to the surface envelope E-protein which was shown to be protective to super-infection with homologous serotype of the virus. Purified recombinant E-protein was made in the baculovirus-Spodo ptera frugiperda expression system. This protein induced neutralizing antib odies in mice. These results prompted us to immunize cynomolgus monkeys (Ma caca fascicularis) with either a live attenuated DEN-2 vaccine or the recom binant E-protein complexed to aluminum hydroxide. After immunization, the m onkeys were challenged with the homologous DEN virus. Serum was collected a t several time points and a virus-specific antibody response including a vi rus neutralizing antibody response was measured. Antibody kinetics and leve ls were similar to those recorded in humans with a natural DEN-virus infect ion. Virus isolation and type specific RT-PCR were performed on the serum s amples. The virus was isolated from sham vaccinated control monkeys but not from monkeys vaccinated with the live attenuated vaccine. One of the two m onkeys immunized with the recombinant E-protein was also protected. Taken t ogether these data indicate the potential of both candidate vaccines and st ress the need for evaluation of different antigen presentation systems for the development of a subunit vaccine approach for DEN. (C) 1999 Elsevier Sc ience Ltd. All rights reserved.