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298 Vaccination against SIV with tat and rev
K. J. Stittelaar1, R. A. Gruters1,2, M. Schutten1, C. A. van Baalen1, G. van Amerongen1, M. Cranage3, P. Liljeström4, G. Sutter5, and A. D. M. E. Osterhaus*1
1Erasmus Med. Ctr., Rotterdam, The Netherlands; 2UMR2142, CNRS/BioMérieux, ENS Lyon, France; 3CAMR, Porton Down, Salisbury, Wilts, UK; 4Microbiology and Tumorbiology Ctr., Karolinska Inst., Stockholm, Sweden; and 5GSF-Inst. of Molecular Virology, Neuherberg, Germany
Immune responses against the regulatory proteins of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) have been associated with efficient resolution of primary viraemia after SIV infection and a benign clinical course of SIV and HIV infection. Here we show that vaccination with vectors expressing the regulatory proteins Tat and Rev enables macaques to more efficiently control SIV replication after challenge than vaccination with the same vectors expressing structural proteins. To this end 12 cynomologous macaques (Macaca fascicularis) were vaccinated with recombinant Semliki Forest virus (6-week interval) and recombinant modified vaccinia virus Ankara (4-week interval) and 5 weeks later challenged with 50 monkey infectious doses 50% of the homologous SIVmac 32H (pJ5). In the current experiment the efficacy of vaccination with Tat and Rev (n = 4), Pol and Gag (n = 4), and control vectors (n = 4) was compared. The control macaques and the Pol and Gag vaccinated macaques all developed plasma viraemia levels similar to those observed in previous SIV infection experiments in these animals. In contrast, in half of the Tat and Rev vaccinated macaques, the plasma viral loads remained below detection (<500 copies/ml), whereas the other 2 showed short-lived and low plasma viraemia. The number of productively infected cells in the peripheral blood of the macaques largely paralleled the kinetics of plasma viraemia, but also indicated that all the macaques were infected with SIV. Collectively, these data show that vaccination with vectors expressing the early regulatory proteins Tat and Rev, but not the late structural proteins Pol and Gag, results in effective control of SIV infection. These observations indicate the importance of specific immunity directed against the early proteins Tat and Rev in controlling viraemia in lentivirus infections. Therefore, the early regulatory proteins should be given serious consideration as HIV vaccine candidates.
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