Local research renews hopes of finding new TB vaccines

For years vaccine developers have struggled to outsmart the tuberculosis germ M. tuberculosis due to its protective power against infection killer cells, known as T-cells, and due to lack of animal models that adequately reflect the human diverse response to the germ. 

So far the only TB vaccine is the 100-year old Bacille Calmette-Guérin (BCG), which offers limited protection and protects infants against severe forms of TB.

But local researchers from the University of Cape Town-based South African Tuberculosis Vaccine Initiative (SATVI), are optimistic they may have made a breakthrough that will pave a way for a new vaccine development that may outmanoeuvre the complex bacteria.

Together with researchers from US-based Stanford University, they have used cutting-edge experimental approaches and sequenced a diverse set of T-cell receptors that recognise the TB germ in infected individuals.

T-cells are an essential component of the immune system, which can detect human cells infected with bacteria or viruses and either destroy these infected cells or help them control the infection.

To recognise such infected cells, T-cells use receptors that recognise small protein fragments from the germ.

During the two-year study, researchers were able to identify differences in the immune response against TB between those who controlled infection (remained healthy) and those who developed TB disease (progressors).

Among the 30,000 TB T-cells identified researchers discovered a subset of T-cells that were associated with study participants who controlled infection and progressors (those who got sick).

In a scientific paper, titled “T cell receptor repertoires associated with control and disease progression following Mycobacterium tuberculosis infection”, which appears in Nature, researchers argue that inducing T-cell responses to these proteins appears to favour control of TB infection “and hence these proteins are thought to be promising targets for inclusion in new TB vaccines”. 

While developing a Covid-19 vaccine, the spike protein which covers and protrudes from the surface of the virus was an obvious target for vaccine development, one of the challenges in finding an effective vaccine for TB concerns its genetic makeup. Not only does it consist of about 4,000 proteins that protect it, but it has a waxy cell membrane that protects the bacterium and the many proteins inside the cell from immune recognition.

Researchers noted previous efforts to identify proteins for vaccine development focused on those known to be secreted out of the bacterial cell, or those targeted by immune responses in animals infected with the germ.

“Determining those parts of the M. tuberculosis bacterium which new vaccine candidates should target is a critical step in the design and development of new TB vaccine candidates,” researchers said.

They say now that the identities of the bacterial protein targets are known, “the next step will be to design candidate mRNA-based vaccines of these proteins and then to determine if these candidate vaccines can protect against M. tuberculosis infection in small animal models”.

This work is being pursued by a collaborative team of researchers from the University of the Witwatersrand/SAMRC Antiviral Gene Therapy Research Unit and the Experimental Tuberculosis and Immunology Research Group at UCT.

“Ultimately, the hope is that this work will result in a highly effective vaccine against TB.”

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