Africa Health Research Institute (AHRI) celebrated three new PhD graduates – Dr Farina Karim, Dr Maphe Mthembu, and Dr Khadija Khan – and a masters graduate, Mahlatse Maseeme, at the September 2023 University of KwaZulu-Natal graduation ceremony.

Dr Maphe Mthembu’s PhD project, supervised by AHRI’s Dr Emily Wong and Prof Thumbi Ndung’u, was titled ‘Immunological profiling of latent TB infection and the impact of HIV infection on immune responses in peripheral blood and lung mucosa’. It focused on profiling latent TB infection (LTBI) using the QuantiFERON assay (gold standard method) between otherwise healthy people living with antiretroviral therapy naïve HIV (PLWH) and those without HIV. Subsequently, she assessed HIV-specific transcriptional effects and how that affected PLWH tuberculosis (TB) immunity.

The QuantiFERON assay was found to underestimate LTBI in PLWH and with a low CD4 T cell count, and Mycobacterium tuberculosis (Mtb)-specific antibodies were found to be a promising alternative measure of LTBI. She also reported an upregulation of transcriptional pathways relating to increased dysfunctional Cytotoxic CD8 T cells in the lung mucosa, suggesting T cell dysregulation as a major mechanism by which HIV immune response alters TB immunity.

Maphe, who worked as a lab technologist in the Wong group at AHRI for five years before going on to do her PhD, grew up in the rural Somkhele area where AHRI has been conducting research for over two decades.

“It feels good to have done my PhD at the research institute which is based in my birthright community,” she said. Through the skills she has gained in HIV and TB immunology, Maphe hopes to continue to contribute solutions to neglected global health challenges stemming from HIV – especially in Africa.

“Latent TB infection (defined as people infected with Mtb but without active TB) remains a controversial topic due to the indirectness of available methods of defining these people in the TB infection spectrum. They do, however, remain one of the global health targets for TB preventative therapy,” said Maphe. “TB is one of the leading causes of death in South Africa, and especially in PLWH. Understanding how HIV immune responses contribute to this is important in designing effective strategies for preventing TB transmission among people living with HIV.”

Dr Farina Karim’s PhD project, titled ‘Effect of HIV status and suppression on SARS-CoV-2 disease severity, vaccine response, and evolution’, explored the effect of SARS-CoV-2 infection on disease dynamics, disease severity, vaccine response, and how prolonged SARS-CoV-2 infection may cause viral evolution in people living with HIV (PLWH). Supervised by AHRI’s Prof Alex Sigal, her research also looked at the difference in disease severity among PLWH in the first and second Covid-19 infection waves in South Africa. Her findings included showing that advanced HIV disease can lead to prolonged SARS-CoV-2 infection and that the associated shedding of infectious virus may result in intra-host evolution of variant mutations. Her studies also demonstrated that SARS-CoV-2 clearance was associated with the emergence of neutralising antibodies and showed that Covid-19 vaccination does induce an increased neutralising antibody response in participants with advanced HIV, but only if HIV viremia is first effectively suppressed with antiretroviral therapy.

“SARS-CoV-2 continues to evolve and affect millions of South Africans while the country still struggles to control the spread of the HIV pandemic. Therefore, it has become increasingly important to understand how these viruses interact with one another to tailor effective interventions,” said Farina.

Read more about some of her research findings in this eLife publication. Farina hopes to further her scientific career and impact public health through translational research.

Dr Khadija Khan’s PhD – which was also supervised by Prof Alex Sigal – explored the effect of hybrid immunity on the neutralising antibody response to emerging SARS-CoV-2 variants, including in people living with HIV. The aim of her study was to identify whether immunity from vaccination – in addition to infection – can lead to additional benefit. She found that hybrid immunity (from vaccination and previous infection) does provide a stronger and broader neutralising antibody response to emerging SARS-CoV-2 variants.

This research resulted in three first-author publications in high impact journals – Clinical Infectious Diseases, Nature and Nature Communications. Kadija’s future research will focus on expanding the knowledge and expertise gained working with SARS-CoV-2 to other viruses.

Mahlatse Maseeme’s masters project, supervised by AHRI’s Dr Al Leslie, looked at how TB disease alone, as well as combined with HIV, (TB-HIV co-infection) impacts the metabolism of immune cells. He did this through studying a pathway of proteins in the mitochondria (powerhouse of the cell) called ‘oxidative phosphorylation’ (OXPHOS). His thesis, titled ‘Flow cytometric assessment of mitochondrial energy complexes in leukocyte subsets during tuberculosis (TB) and TB-HIV coinfection’, explored the importance of immune cells in fighting TB and how they rely on certain aspects of the metabolism for help. One of these is OXPHOS, which supplies energy – among other biological processes – needed during an immune response.

“Knowing which aspect of metabolism is impacted by or linked to TB can be useful for uncovering potential metabolic biomarkers for host-directed therapies, or even for treatment response,” said Mahlatse. He plans to expand on this project by adding some more data and publish the work while continuing with other projects for his PhD and public engagement.

(Top photo: Dr Farina Karim, Dr Khadija Khan, Dr Maphe Mthembu and Mahlatse Maseeme)