SIMIAN IMMUNODEFICIENCY VIRUS-DNA VACCINE TRIAL IN MACAQUES

An experimental vaccine consisting of five DNA plasmids expressing dif ferent combinations and forms of simian immunodeficiency virus-macaque (SIVmac) proteins has been evaluated for the ability to protect again st a highly pathogenic uncloned SIVmac251 challenge. One vaccine plasm id encoded nonreplicating SIVmac239 virus particles. The other four pl asmids encoded secreted forms of the envelope glycoproteins of two T-c ell-tropic relatives (SIVmac239 and SIVmac251) and one monocyte/macrop hage-tropic relative (SIVmac316) of the uncloned challenge virus. Rhes us macaques were inoculated with DNA at 1 and 3, 11 and 13, and 21 and 25 weeks. Four macaques were inoculated intravenously, intramuscularl y, and by gene gun inoculations. Three received only gene gun inoculat ions. Two control monkeys were inoculated with control plasmids by all three routes of inoculation. Neutralizing antibody titers of 1:216 to 1:768 were present in all of the vaccinated monkeys after the second cluster of inoculations. These titers were transient, were not boosted by the third cluster of inoculations, and had fallen to 1:24 to 1:72 by the time of challenge. Cytotoxic T-cell activity for Env was also r aised in all of the vaccinated animals. The temporal appearance of cyt otoxic T cells was similar to that of antibody. However, while antibod y responses fell with time, cytotoxic T-cell responses persisted. The SIVmac251 challenge was administered intravenously at 2 weeks followin g the last immunization. The DNA immunizations did not prevent infecti on or protect against CD4(+) cell loss. Long-term chronic levels of in fection were similar in the vaccinated and control animals, with 1 in 10,000 to 1 in 100,000 peripheral blood cells carrying infectious viru s. However, viral loads were reduced to the chronic level over a short er period of time in the vaccinated groups (6 weeks) than in the contr ol group (12 weeks). Thus, the DNA vaccine raised both neutralizing an tibody and cytotoxic T-lymphocyte responses and provided some attenuat ion of the acute phase of infection, but it did not prevent the loss o f CD4(+) cells.