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.
Fields of science
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistance
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Topic(s)
Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
2000 Antwerpen
Belgium