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EPI-VAC


HIV/AIDS

Identification of Novel Epitopes as HIV-1 Vaccine Candidates
Framework programme:
6
Call:
2
Project number:
LSHP-CT-2005-012168
EC contribution:
€ 911,050
Duration:
24 months
Type:
STREP
Starting date:
June 2005

Keywords: HIV-1; immunogenic epitopes; AIDS vaccine

Summary:

The aim of this project is to select peptide epitopes that mimic neutralisation-sensitive domains of HIV-1 envelope and may function as candidate HIV-1 vaccines. To date, efforts to develop a truly prophylactic HIV-1 vaccine have been hindered by difficulties in identifying immunogens that elicit broadly neutralising antibodies. This lack of significant cross-protection raises further concerns on the capacity of classical Env-based vaccines to afford substantial protection against field isolates. Indeed, current unmodified gp120 or gp140 envelope-based vaccines in human subjects have shown little or no protection from heterologous HIV-1 isolates such as would be encountered in the field. This indicates that vaccine trials with currently available immunogens will afford low percentages of protection with a large number of vaccine breakthroughs and will raise ethical and financial issues concerning the treatment of any volunteers who become infected. It is of the highest priority that a focused effort is undertaken to develop novel Env antigens capable of inducing broad and potent neutralising antibodies to a wide variety of strains. Consistently, this consortium is developing a new generation of Env antigens based on complex but conserved epitopes to induce broad neutralising antibodies. This objective will be achieved by two complementary strategies: (i) screening of random peptide libraries with novel MAbs that neutralise primary HIV-1 isolates assigned to distinct clades; (ii) designing 30-40 amino acid peptides that mimic discontinuous regions of gp120 and gp41 that are sensitive to neutralisation by antibodies and are conserved among HIV strains of distinct clades. These include the CD4-binding domain, the bridging sheet and the pre-fusogenic harpin loop of gp41. During this two-year proposal the novel vaccine candidates will be validated in mice; however, the Consortium is endowed with the facilities and resources to proceed to monkey models of HIV-1 infection.

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