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A synergistic effect of a combined bivalent DNA-protein anti-HIV-1 vaccine containing multiple T- and B-cell epitopes of HIV-1 proteins.

Bazhan SI, Karpenko LI, Lebedev LR, Uzhachenko RV, Belavin PA, Eroshkin AM, Ilyichev AA

Theoretical Department, State Research Center of Virology and Biotechnology Vector, 630559 Koltsovo, Novosibirsk Region, Russia. bazhan@vector.nsc.ru

Immunogenic properties of the combined vaccine CombiHIVvac, comprising polyepitope HIV-1 immunogens, one being the artificial polyepitope protein TBI, containing the T- and B-cell epitopes from Env and Gag proteins, and the DNA vaccine construct pcDNA-TCI coding for the artificial protein TCI, carrying over 80 T-cell epitopes (both CD4+ CTL and CD8+ Th) from Env, Gag, Pol, and Nef proteins, are studied in this work. The data reported demonstrate clearly that a combination of two B- and T-cell immunogens (TBI and TCI) in one construct results in a synergistic increase in the antibody response to both TBI protein and the proteins from HIV-1 lysate. The level of antibodies induced by immunization with the constructs containing either immunogen alone (TBI protein or the plasmid pcDNA-TCI) was significantly lower as compared to that induced by the combined vaccine. The analysis performed suggests that the presence of CD4+ T-helper epitopes, which can be presented by MHC class II, in the protein TCI may be the main reason underlying the increased synthesis of antibodies to TBI protein due to a CD4-mediated stimulation of B-cell proliferation and differentiation.

Published 8 October 2007 in Mol Immunol, 45(3): 661-9.
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