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Study of hiv-1 variability in Cameroon and Gabon. Implications for vaccine and antivirale intervention strategies

Objective

* To provide a surveillance system for newly emerging and naturally occurring recombinant HIV-1 strains in Cameroon and Gabon.
* To classify sera from HIV infected individuals according to their capacity to neutralize primary isolates representing different genetic clades.
* To characterize broadly neutralizing antibodies and epitopes in individuals infected with HIV-1 of different genetic subtypes, and evaluate the role they play in disease protection.
* To investigate the susceptibility of HIV-1 strains belonging to different genetic clades, to both existing and experimental anti-HIV compounds and to provide a surveillance system for emerging strains of HIV-1 with naturally occurring mutations conferring antiviral drug resistance.
* To optimize the quantification of HIV RNA in plasma of patients infected with different types, subtypes and recombinant subtypes of HIV.
Expected Outcome

* Making available to developing countries a simple economical serologic test to monitor circulating HIV-1 subtypes.
* Since only a limited number of key isolates are required to document the broad cross-clade neutralization capacity of a particular serum, we hope in future to be able to monitor the efficacy of HIV-1 vaccines inducing high-titer cross-neutralizing antibodies in an economic way.
* To enable some research centres in Cameroon and Gabon to solve some of their specific problems, such as the impact of the extreme high genetic variability of HIV on anti-HIV drug susceptibility as well as on the characterization of conserved neutralization epitopes; discovery of new, not yet identified HIV subtypes and recombinant viruses naturally occurring; development of antiviral drugs efficient against the predominant HIV-1 subtypes circulating in developing countries.
* Both heteroduplex mobility assay (HMA) on PCR amplified fragments generated from HIV RNA in serum or plasma of HIV infected individuals and V3-peptide ELISA will be used to monitor the prevalence of different genetic subtypes of HIV-1.
* HMA on both gag and env fragments of the same isolate will allow to study the prevalence of recombinant viruses.
* Susceptibility of the different subtypes and the natural recombinant viruses towards various HIV inhibitors will be determined.
* Neutralizing antibody patterns in sera of individuals infected with all subtypes (A-H) within group M and representatives of group O to their homologous and heterologous primary isolates will be documented using a peripheral blood mononuclear cell based neutralization assay.
* Neutralization data will be analyzed by a multivariate (spectral mapping) analysis.
* Chimeric viruses consisting of neutralization sensitive and insensitive primary HIV-1 strains will be constructed in order to characterize the epitopes playing a role in the neutralization process.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Instituut voor Tropische Geneeskunde Prins Leopold
Address
155,Nationalestraat 155
2000 Antwerpen
Belgium

Participants (4)

Institut de Recherche pour le Développement
France
Address
Avenue Agropolis 911
34032 Montpellier
Ministère de la Santé Publique
Gabon
Address

30 Libreville
Tibotec NV
Belgium
Address
661,Dire Eikenstraat 661
2650 Edegem
University of Yaoundé I
Cameroon
Address
Melen Street
10 Yaoundé