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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/11026 |
| Date | 17 January 2012 |
| Creators | Naidoo, Thenusha |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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