16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

VACCINE INDUCED T-CELL RESPONSES IN IMMUNISED RHESUS MACAQUES CORRELATE WITH SIV REPLICATION KINETICS IN VITRO BUT NOT IN VIVO

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. WeAa0204

Ochieng' W., Stahl-Hennig C., Suh Y.-S., Sopper S., Hunsmann G., Sauermann U.
German Primate Centre, Virology and Immunology, Goettingen, Germany

BACKGROUND: Non-human primates provide an excellent model for AIDS research. Here, we describe the relationship between individual in vitro SIV replication (VVR), respective vaccine-induced immunological responses and clinical outcome in a pre-clinical vaccine study.

METHODS: 18 rhesus monkeys were divided into 3 groups; Group-1 (n=6) served as non-immunised controls; Groups-2 (n=6) and 3 (n=6) were DNA primed and received SIV-adenovirus boost through different routes. All animals were challenged with SIVmac239 at 44 weeks post immunisation (wpi). Cellular immune response at baseline, two weeks after each booster immunization and at the time of challenge was determined by IFN-γ ELISPOT. As a read-out for the capacity of immune response to restrict viral replication in vitro, PBMCs were stimulated with Con-A overnight before infection with SIVmac239 at an MOI of 0.003 and maintained for 2 weeks in culture medium supplemented with Interleukin-2. Viral loads in culture supernatants and in plasma after challenge were analysed by real-time PCR.

RESULTS: Strong T cell responses were elicited following booster immunizations, but declined 4 weeks after last boost until day of challenge. These responses correlated strongly with VVR for vaccinees (p=0.002). At baseline, VVR was comparable in all groups and remained stable for controls. In contrast, VVR in vaccinees declined significantly during immunisation until 2 weeks after last boost. At this time-point, VVR in group 3 was 100-fold lower compared to controls and correlated strongly with number of IFN-γ producing cells. At challenge, the differences in VVR between groups waned. Post-challenge peak but not set-point viremia was significantly lower for all immunised than control animals (p=0.006).

CONCLUSIONS: SIV replication in vitro correlates with vaccine-induced T cell responses and shows "immunisation-route-dependent" kinetics. This kinetics was predictive of post-challenge outcome and may be useful in designing pre-clinical vaccine and pathogenesis studies. Additional factors worth investigation may influence in vitro vaccine response.

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2006-08-13
WeAa0204

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