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1 Laboratory of Virology, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy
2 Department of Virology, Biomedical Primate Research Center, PO Box 3306, 2280 GH Rijswijk, The Netherlands
3 Laboratory of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Viale R. Elena 299, 00161 Rome, Italy
4 Microbiology and Tumor-Biology Center, Karolinska Institute, Box 280, S-17177 Stockholm, Sweden
5 AIDS Immunopathogenesis and Vaccine Development, Robert Koch Institute, 13353 Berlin, Germany
Correspondence
Fausto Titti
titti{at}iss.it
We investigated the protective efficacy of a systemic triple vector (DNA/rSFV/rMVA)-based vaccine against mucosal challenge with pathogenic simian immunodeficiency virus (SIV) in cynomolgus monkeys. Animals were immunized at week 0 with DNA (intradermally), at weeks 8 and 16 with recombinant Semliki Forest virus (rSFV, subcutaneously) and finally, at week 24, with recombinant modified vaccinia virus Ankara strain (rMVA, intramuscularly). Both DNA and recombinant viral vectors expressed a wide range of SIV proteins (Gag, Pol, Tat, Rev, Env and Nef). This immunization strategy elicited cell-mediated rather than humoral responses that were especially increased following the last boost. Upon intrarectal challenge with pathogenic SIVmac251, three of the four vaccinated monkeys dramatically abrogated virus load to undetectable levels up to 41 weeks after challenge. A major contribution to this vaccine effect appeared to be the T-cell-mediated immune response to vaccine antigens (Gag, Rev, Tat, Nef) seen in the early phase of infection in three of the four vaccinated monkeys. Indeed, the frequency of T-cells producing antigen-induced IFN-
mirrored virus clearance in the vaccinated and protected monkeys. These results, reminiscent of the efficacy of live attenuated virus vaccines, suggest that vaccination with a combination of many viral antigens can induce a robust and stable vaccine-induced immunity able to abrogate virus replication.
These authors contributed equally to this work.
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