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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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.
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Expert Review of Vaccines (2019)
Journal of Clinical Investigation (2019)
Induction of neutralizing antibodies against tier 2 human immunodeficiency virus 1 in rhesus macaques infected with tier 1B simian/human immunodeficiency virus
Archives of Virology (2019)
Viral vector and route of administration determine the ILC and DC profiles responsible for downstream vaccine-specific immune outcomes