AEGiS-15IAC: HIV Epidemic Profile in Russia and Preparing for Clinical Trials of the First Russian HIV Vaccine "VICHREPOL".

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

HIV Epidemic Profile in Russia and Preparing for Clinical Trials of the First Russian HIV Vaccine "VICHREPOL".

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10210)

Nikolaeva I, Korobova S, Chevalier A, Ignatjeva G, Karamov E, Kornilaeva G, Pavlova T, Vorobjova M, Savinova I, Nekrasov A, Ivanova A, Gudima G, Khaitov R, Sidorovich I
Institute of Immunology, RF Ministry of Health, Moscow, Russian Federation

BACKGROUND: In Russia, >89 % of >250 000 documented cases of HIV infection caused by IDU. This should be taken in account when domestic trials cohorts are sought. First Russian candidate anti HIV vaccine VICHREPOL based on recombinant protein rec(24-41) (HIV1 p24 + fragment of gp41), conjugated with novel potent safe immunomodulator polyoxidonium (PO) (approved for use in humans) was prepared, immunogenicity and safety of the vaccine were assessed in pre-clinical study.

METHODS: Immunogenicity of VICHREPOL was assessed in ELISA, WB, antigen (Ag)-dependent proliferation and neutralizing antibody (Ab) assays. Safety was evaluated by general safety and rabbit pyrogen assays. For acute toxicity, vaccine was administered (500 mcg protein/mouse) once, i/p; for chronic toxicity, at doses 1 and 50 mcg protein/mouse daily during 14 days. For immunogenicity, mice (CBAxC57/B16, 20/group) were immunized i/p twice, at dose 50 mcg protein/mouse. Ag determinants of vaccine recombinant protein were compared with those of virus prototype with ELISA, using sera of HIV infected patients and anti p24 Abs developed in sheep.

RESULTS: Sera of vaccinated mice (1:50) neutralized HIV1 in culture (NI=55 %). Ag-specific proliferative index was 10 ([3H]-thymidine incorporation). VICHREPOL induced Ag-specific Abs (ELISA titers>50 000). Abs elicited against vaccine in mice recognized HIV1 culture derived gp41 and p24 in WB, while Abs from sera of HIV infected patients & sheep anti p24 Abs recognized VICHREPOL in ELISA and WB. Vaccine was well tolerated, apyrogenic, no inflammatory reactions, nor morphological, histological, biochemical and functional disorders were found.

CONCLUSION: Pre-clinical studies demonstrated immunogenicity & safety of candidate vaccine VICHREPOL with built-in adjuvant PO. RF Ministry of Health approval of clinical trials Phase I pending. Basing on HIV epidemic profile in Russia, work with an injection drug user cohort is being prepared.

Keywords: AEGIS, AIDS Vaccines, Acquired Immunodeficiency Syndrome, HIV Seropositivity, HIV-1, Clinical Trials, HIV Infections, Russia, Enzyme-Linked Immunosorbent Assay, Adjuvants, Immunologic, Abscess, Recombinant Proteins, Humans, Animal, Mice, Rabbits

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A10210