Africa Health Research Institute (AHRI) faculty members Professor Zaza Ndhlovu and Dr Mohlopheni Jackson Marakalala have each been awarded prestigious Bill & Melinda Gates foundation Grand Challenges grants to support their respective projects aiming to address the major obstacles of HIV cure, and to find new strategies to enhance tuberculosis (TB) vaccines.

Launched in 2003, the Grand Challenges in Global Health Grant is an initiative of the Bill & Melinda Gates foundation that promotes the solving of crucial global health and development problems through innovation. The focus of this initiative is on 14 major scientific challenges that may lead to crucial advances in preventing, treating, and curing diseases in the developing world if solved.

Professor Zaza Ndhlovu’s work is on cellular immune responses to HIV-1, with the ultimate goal of contributing to the development of an HIV vaccine. Current HIV therapy does not cure HIV because some of the virus hides in cells in certain parts of the body where the current HIV drugs do not penetrate well. Additionally, CD8 lymphocytes – a type of white blood cell in the immune system which destroy virus infected cells –are restricted from accessing these tissues. Through his new Grand Challenges grant, Ndhlovu aims to address these issues by identifying means of enhancing immune responses in tissues where HIV tends to hide to evade detection and elimination by the immune system. Essentially, Ndhlovu’s project seeks to modulate the immune system so it can fight HIV more effectively. He will do this by developing new methods of promoting the access of CD8 lymphocytes into tissue sanctuary sites where they are needed to eliminate persistent HIV infection.

Ndhlovu’s project is in collaboration with Dr Fikadu Tafesse from Oregon Science University (OHSU) in the USA. Through this collaboration, Ndhlovu’s lab members will be provided with training opportunities at OHSU and transfer cell engineering technology to Ndhlovu’s lab at AHRI.

“If successful, this work will benefit millions of people currently on life-long HIV treatment, particularly in South Africa, which is home to more than 20% the global population on lifelong antiretroviral therapy,” said Ndhlovu.

Dr Mohlopheni Marakalala’s research is focused on developing TB biomarkers and host-directed therapies by studying factors associated with disease progression using lung tissue and blood samples from TB patients. The success of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB, lies in its ability to survive and replicate within human cells. Recent studies have identified mycobacterial genes, called ‘counteractome’, which enable the bacterium to survive and evade specific arms of the immune system. Understanding and targeting these survival strategies will help with exploring new therapeutic interventions that can disarm the bacterium and heighten the killing capacity of the immune system and vaccine-mediated responses.

For his project, Marakalala and his team will use Tn-Seq – a genetic screening tool that identifies bacterial genes that are specifically required to survive in the presence of intact immune system -to identify and validate mycobacterial genes specifically required to survive BCG-induced trained immunity in blood from vaccinated participants. The outcomes of Marakalala’s project will provide an understanding of mechanisms that assist the TB-causing bacteria to resist the immune system. Such mechanisms will be targeted for drugs that will synergise with the BCG-induced immune system in killing the TB bacteria.

Marakalala’s project is in collaboration with Professor Eric Rubin’s laboratory at Harvard TH Chan School of Public Health. As part of the project, one of Marakalala’s team members will spend some time learning Tn-Seq at Harvard University.

Marakalala says that being a recipient of the grant provides a unique opportunity for him to explore the concept of vaccine-potentiating therapy.

“Receiving this grant gives me an opportunity to contribute towards AHRI’s vision which seeks to eliminate the TB disease,” he said.

Top photo: Prof Zaza Ndhlovu and Dr Mohlopheni Marakalala 

– Story by Yasmine Mamboleo