Understanding why HIV-exposed infants may be prone to infections

If ever you had the opportunity to visit a primary health clinic (PHC) in South Africa, you would find rows and rows of mothers cradling their little ones eagerly waiting in line to be attended to by the nurses. Among these little ones, you could possibly find a 6-month-old boy named Sam. With his bright eyes and curious smile, Sam is now a regular at the PHC, often being treated for a cold or skin condition.

Researchers from the University of Cape Town's Institute of Infectious Disease and Molecular Medicine (IDM), along with local and international colleagues, investigated the early life challenges of babies exposed to HIV before birth. Their focus was on the immune system development during the crucial first months of life of babies who did not contract the disease but were born to women living with HIV. Their findings, published in Nature Communications, uncovered some surprising truths.

It has been known for some time that babies like Sam face a higher risk of infections compared to those who were neither exposed to HIV before birth nor infected. However, this research reveals the reason why: Sam's immune system, like many others, was subtly affected even before birth.

Leading this research was IDM Fellow Dr Sonwabile Dzanibe. His team discovered that infants exposed to HIV in the womb had less variety in their T cell receptors (TCRs), which are the very tools their immune systems use to recognise and fight off different pathogens. This means that Sam's immune system isn't as prepared to combat the wide range of germs he will encounter compared to other children who were never exposed to the virus.

The study was overseen by senior author and IDM Adjunct Member, Professor Emeritus Clive Gray, and co-authored by IDM Member Associate Professor Heather Jaspan, along with experts from Stanford University and Stellenbosch University. Their combined efforts revealed that the reduced variety in TCRs among these infants’ naïve T cells (the ones that haven’t yet encountered diseases) leads to slower development of memory T cells. These memory T cells are essential for a quick response to previously encountered infections.

Importance of understanding immune systems

Dr Dzanibe, a fellowship awardee of both Wellcome and the South African Medical Research Council, focuses his research on investigating the development of immune systems of infants and factors that influence early childhood vaccines. More specifically on the development of vaccines aimed at reducing infectious diseases in children.

“These results highlight how early life events, those occurring even before birth, play a significant role in the development of the immune system,” said Dzanibe. “Understanding the impact of these events is crucial when designing vaccines for newborns.”

This research is particularly important for countries like South Africa, where a significant number of babies are born to women living with HIV. According to the 2019 National Antenatal HIV Sentinel Survey, the prevalence of HIV among pregnant women has stayed around 30% since 2004. Babies like Sam, while not infected with HIV, still face more frequent and severe infections due to their unique immune challenges.

 

These results highlight how early life events, those occurring even before birth, play a significant role in the development of the immune system.

This work highlights the urgent need for more research and targeted healthcare strategies to protect these vulnerable infants.

Read the full article: Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants.

So, the next time you visit a clinic, think of little Sam and the unseen battles his immune system is preparing to fight, and the dedicated researchers working to give him and others like him a fighting chance.