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Cross-protection against mucosal simian immunodeficiency virus (SIVsm) challenge in human immunodeficiency virus type 2-vaccinated cynomolgus monkeys

Swedish Institute for Infectious Disease Control and Microbiology and Tumour Biology Centre, Karolinska Institute, SE-17182 Solna, Sweden¹
Immunopathology Laboratory, Karolinska Institute, SE-10401 Stockholm, Sweden²
Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands³

Author for correspondence: Lilian Walther-Jallow at Department of Immunology, Swedish Institute for Infectious Disease Control, SE-17182 Solna, Sweden. Fax +46 8 337460. e-mail Lilian.Walther.Jallow{at}mtc.ki.se

In this study we compared the efficacy of live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine alone versus boosting with live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol). Six monkeys were first inoculated intravenously with live HIV-2_SBL-6669 and 7 to 10 months later were challenged intrarectally with 10 MID₅₀ of cell-free simian immunodeficiency virus (SIV) strain SIVsm. One monkey was completely protected against SIV infection and all five monkeys that became SIV-infected showed a lower virus replication and an initial lower virus load as compared with a parallel group of six control animals. In another experiment five monkeys were immunized either three times with ALVAC HIV-2 alone or twice with ALVAC HIV-2 and once with purified native HIV-2 gp125. The monkeys were then challenged with HIV-2 given intravenously and finally with pathogenic SIVsm given intrarectally. After challenge with SIVsm, three of five monkeys were completely protected against SIVsm infection whereas the remaining two macaques became SIV-infected but with limited virus replication. In conclusion, vaccination with an ALVAC HIV-2 vaccine followed by exposure to live HIV-2 could induce cross-protection against mucosal infection with SIVsm and seemed to be more efficient than immunization with a live HIV-2 vaccine only.