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Content archived on 2022-12-23

Development of virus-like particle (VLP) candidate for HIV produced by baculo multi-gene expression Vectors

Objective

The aim of the project is to evaluate the use of multipromotor baculovirus virus-like particle (VLP) technology for the generation of VLPs as candidate vaccines of human infectious agents, in particular the Human ImmunoDeficiency Virus (HIV-1).

VLP technology based on the use of the baculo multigene expression system, enables the design of novel immunogens composed of a number of important viral antigens in a non-infectious state to confer protection. The possibility of incorporating multiple antigens in a single eukaryotic baculo expression transfer vector make VLPs mimic viruses in terms of structure, antigenicity and immunogenicity. Their way of presenting viral antigens to the immune system may therefore result in a more adequate response than when presented as single purified agents. Results obtained for animal viruses, e.g. Bluetonge virus, with baculo multigene expression vectors, form the basis for this approach.

The project will comprise different phases, which are briefly described below:

Phase 1: the first target of this project is the production of VLPs for HIV.
Constructs will be prepared allowing both the expression of the individual genes (for the preparation of standard in the analyses of VLPs) as well as the expression of a number of selected viral components which represent the proteinaceous compounds of the wild-type virus (VLPs).

Phase 2: the recombinant particles produced will be identified and analysed immunologically as well as physicochemically and will be compared to the wild-type virus. A broad panel of polyclonal and monoclonal antisera which are already available, will allow the initial serological characterisation (ELISA, western blotting, etc.) of putative recombinant viral proteins.

Phase 3: the production and purification of the VLPs for HIV will be optimized and scaled up to a high level in order to investigate the efficacy of these VLPs as candidate vaccines.

Phase 4: HIV VLPs will be evaluated for their effectiveness as potential (human) vaccines. At first T-cell and B-cell responses will be investigated in an in vivo mouse model. The human T-cell response will be evaluated in vitro by T-cell proliferation assays. The testing will finally include challenging experiments in chimpanzees where protection will be examined by seroconversion, polymerase chain reaction (PCR) analysis or virus culture.

If phases 1 to 4 are successful, patents will be applied for, and collaboration will be pursued with other partners to enter clinical trials in this project (Phase 5). For the moment, this project does not include clinical trials and research other than that described in the contract CTT-535 of the VALUE programme.

Topic(s)

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Call for proposal

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Funding Scheme

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Coordinator

INSTITUTO DE BIOLOGIA EXPERIMENTAL E TECNOLOGIA
EU contribution
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Address
APARTADO 12
2780 OEIRAS
Portugal

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Total cost
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Participants (2)