Since the human immunodeficiency virus (HIV) epidemic in the 1980s, great strides have been made regarding drug therapeutics, which has slowed the progression of HIV to AIDS and decreased the mortality rates in HIV patient populations. Other prevention interventions, such as pre-exposure prophylaxis (PrEP), have also contributed immensely to reducing HIV infections. However, today in many parts of the world, especially in sub-Saharan Africa, HIV is still prevalent. This demonstrates the need to focus on more long-term preventative interventions, such as vaccines. In order to do this, more research has to be conducted on the B cell adaptive immune response to HIV. This thesis research explores how the opportunistic disease tuberculosis, which is present in many HIV-positive patients, affects B cell survival in these HIV patients. Our methods section consists of CD14+ cell isolation and MDM culture experiments that we performed and subsequent planned experiments that we are yet to complete. These experiments include infecting MDM cultures with a double pseudotyped VSVg-NL43 HIV. We will also expose the MDMs to the TB antigen, lipomannan (LM), to represent HIV/TB co-infection in vitro. LM is a toll-like receptor 2 (TLR2) agonist. The MDM cultures will enable us to measure the amount of BAFF and APRIL mRNA produced in the HIV, HIV/LM, and LM MDM cultures using RT-PCR. Using a growth curve, we will observe BAFF and APRIL's effects on the survival of B cells in the different MDM cultures. We hypothesize that the TB antigen will increase B-cell survival through the BAFF system molecules in HIV patients. The results of our research will provide insights on the role TB plays in enhancing the humoral immune response in HIV-1 patients, paving the way for further research on understanding the mechanism responsible for this and consequently creating vaccine and vaccine adjuvant opportunities.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43323 |
| Date | 09 November 2021 |
| Creators | Asante, Phoebe Ohemah |
| Contributors | Sagar, Manish, Franzblau, Carl |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution 4.0 International, http://creativecommons.org/licenses/by/4.0/ |
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