Identification and characterization of HIV-1 specific neutralizing antibodies from HIV-1 seropositive patients and autoimmune (HIV-1 seropositive or seronegative) participants.

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dc.contributor.author Naidoo, Thenusha
dc.date.accessioned 2012-01-17T09:10:43Z
dc.date.available 2012-01-17T09:10:43Z
dc.date.issued 2012-01-17
dc.identifier.uri http://hdl.handle.net/10539/11026
dc.description.abstract Since the discovery of HIV-1, the production of an effective prophylactic or therapeutic vaccine remains elusive. An effective vaccine must be able to elicit a potent humoral and cellular immune response. Neutralizing antibodies target the envelope glycoproteins on the surface of HIV-1 virions thereby preventing viral entry. Unfortunately, to date only a handful of neutralizing antibodies have been identified that are capable of neutralizing different viral strains within diverse subtypes, and none have been isolated from HIV-1 subtype C infected patients. In this study, we screened four different HIV-1 subtype C infected patient cohorts for the presence of neutralizing antibodies against a panel of 5 subtype C and 1 subtype B pseudovirus/es in a pseudovirion based neutralizing antibody assay. The CT cohort comprised 9 slow progressor plasma samples, the FV cohort consisted of 11 antiretroviral drug naïve HIV-1 subtype C infected plasma samples. Plasma samples from 10 antiretroviral treatment experienced HIV-1 subtype C infected patients failing first line therapy made up the DR cohort and the JM cohort consisted of 10 serum samples from HIV-1 seropositive or seronegative individuals with an autoimmune disorder. A pseudovirion neutralizing antibody assay was successfully established, and all plasma and serum samples were heat inactivated and screened using this assay. Analysis of the percentage neutralization and IC50 data showed no correlation between the presence of neutralizing antibodies and delayed disease progression in the SP cohort. High levels of neutralizing antibodies were observed in the DR cohort, however future studies are required to confirm if the measured neutralization is due to residual antiretroviral drugs in the plasma or neutralizing antibodies. No samples within the FV cohort showed promising neutralizing antibody activity however the JM cohort harboured 3 serum samples (TN5, TN6 and TN8) that exhibited a greater than average breadth of neutralization and are worth investigating further in future studies. Patients TN5, TN6 and TN8 were all HIV-1 positive with an additional autoimmune disease. The availability of stored bone marrow samples for TN5, TN6 and TN8 will allow for the generation of antibody phage display libraries and isolation of monoclonal antibodies, with potentially broadly cross reactive activity. en_US
dc.language.iso en en_US
dc.subject.mesh HIV-1 en-US
dc.subject.mesh
dc.title Identification and characterization of HIV-1 specific neutralizing antibodies from HIV-1 seropositive patients and autoimmune (HIV-1 seropositive or seronegative) participants. en_US
dc.type Thesis en_US


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    Thesis (Ph.D.)--University of the Witwatersrand, 1972.

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