Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity

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Abstract

Recent studies of human immunodeficiency virus type 1 (HIV-1) infection in humans and of simian immunodeficiency virus (SIV) in rhesus monkeys have shown that resolution of the acute viral infection and control of the subsequent persistent infection are mediated by the antiviral cellular immune response1,2,3,4,5,6,7,8,9,10,11. We comparatively assessed several vaccine vector delivery systems—three formulations of a plasmid DNA vector, the modified vaccinia Ankara (MVA) virus, and a replication incompetent adenovirus type 5 (Ad5) vector—expressing the SIV gag protein for their ability to elicit such immune responses in monkeys. The vaccines were tested either as a single modality or in combined modality regimens. Here we show that the most effective responses were elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector. After challenge with a pathogenic HIV–SIV hybrid virus (SHIV), the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the virus infection. The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine.

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Figure 1: Quantification of CD8+ T-cell responses by tetramer analysis during immunization.
Figure 2: Post-challenge viraemia and CD4+ T-cell counts.

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Acknowledgements

We gratefully acknowledge K. Wright of Laboratory Animal Resources, Merck Research Laboratories, R. Druilhet and R. Colligan of New Iberia Research Center, and M. Hevy and K. Manson of Primedica for their contributions to this research. We are also thankful for assistance from B. Moss and V. Hirsch of the NIH in constructing the recombinant MVA virus.

Author information

Correspondence to Emilio A. Emini.

Supplementary information

Table 1, methods and figure legend (DOC 38 kb)

Figure 1 (GIF 28 kb)

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