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Vaccibodies for SIV: a step towards an HIV vaccine for humans.

Tildelt: kr 3,1 mill.

Aim: Vaccibodies are recombinant vaccine molecules that can target antigen presenting cells (APC) and enhance immune responses towards the delivered antigen. The primary objective of the present proposal is to develop Vaccibodies for simian immunodeficien cy virus (SIV) and to test whether they enhance anti-viral CD8+ T cell responses in mice. Given that the tests in mice generate promising results, our next goal is to evaluate the SIV-Vaccibody format in macaques. The long-term goal is to extend the Vacci body strategy to humans. Background: The Bogen group has described a novel type of recombinant vaccine molecule (Vaccibody) that targets APC for efficient delivery of antigen and induction of strong protective immune responses in mice. Recently, we observ ed that Vaccibodies that target chemokine receptors (CCR) enhanced the number of HIV-specific CD8+ T cells (Øynebråten et al., unpublished). Projects of the proposal: The projects of the proposal is based on the premise that MIP-1a has been particularly effective in our mouse experiments for induction of CD8+ T cells. Moreover, human MIP-1a Vaccibodies can be tested in mice and monkeys because of cross reactive binding to CCR. Projects: (i) Construction of SIV Gag antigen-containing Vaccibodies with huma n MIP-1a as targeting units. (ii) Evaluation of the immunogenicity of the SIV Gag Vaccibody in mice. (iii) Efficacy testing and challenging studies in nonhuman primates. (iv) Extension of the Vaccibody format to humans. Budget: Salary for young investigat or for three years, overseas research grant (Barouch lab), and consumables. Project management: Experiments in mice will be performed by the applicant IØ in Bogen lab (CoE CIR, Univ. of Oslo). Monkey experiments are planned to be done at New England Prima te Research Center/Barouch lab. Extension to humans involve Prof. Dag Kvale (Oslo University Hospital, Ullevål). A Norwegian biotech company, Vaccibody AS, has filed a patent on Vaccibodies and will handle IPR.

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