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Identification of novel HIV-1 epitopes as vaccine candidates

Objective

The aim of this project is to select peptide epitopes that mimic neutralization 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 difficult y in identifying immunogens that elicit broadly neutralizing 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, curr ent 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 wi ll 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 undertak en 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: a. Screening of Random Peptide Libraries with novel MAbs that neutralise primary HIV-1 isolates assigned to distinct clades; b. designing of 30-40 amino acid peptide s that mimic discontinuous regions of gp120 and gp41 that are sensitive to neutralization 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 gp 41. In this two years proposal the novel vaccine candidates will be validated in mice; however, the Consortium is endowed with the facilities and resources to proceed to monkeys models of HIV-1 infection.

Call for proposal

FP6-2003-LIFESCIHEALTH-3
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Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

UNIVERSITÀ DI NAPOLI FEDERICO II- DIPARTIMENTO DI BIOCHIMICA E BIOTECNOLOGIE MEDICHE
Address
Via S. Pansini 5
Napoli
Italy

Participants (3)

FOUNDATION BIOMEDICAL PRIMATE RESEARCH CENTRE
Netherlands
Address
Lange Kleiweg 139
Rijswijk
POLYMUN SCIENTIFIC IMMUNBIOLOGISCHE FORSCHUNG GMBH
Austria
Address
Nussdorfer Laende 11
Vienna
UNIVERSITY OF APPLIED LIFE SCIENCES AND NATURAL RESOURCES
Austria
Address
Muthgasse 18B
Vienna