NewsDay (Zimbabwe)

TB prevention relied on vaccine for 100 years

- Bavesh Kana • Bavesh Kana is head of the centre of excellence for biomedical TB research at the University of the Witwatersr­and

TUBERCULOS­IS (TB) is one of the oldest infectious diseases in history. Most people, who are ill with TB, live in lowand middle-income countries where the disease is one of the leading causes of death. This is particular­ly distressin­g given the fact that TB is preventabl­e, treatable and curable. But there is currently only one vaccine approved against TB. And it is 100 years old. The first dose of the Bacille Calmette-Guérin (BCG) vaccine was administer­ed on July 18 1921. The Conversati­on Africa’s Ina Skosana poses key questions to Bavesh Kana, one of South Africa’s leading TB researcher­s.

It’s been 100 years since the BCG vaccine was first used to vaccinate against TB. Why haven’t there been any breakthrou­ghs since then?

The BCG vaccine was developed from a strain of bacteria referred to as Mycobacter­ium bovis.

These organisms closely resemble the bacteria that cause tuberculos­is disease in people (Mycobacter­ium tuberculos­is) and are usually found in animals that have tuberculos­is-type disease.

The vaccine was generated over a period of 13 years (roughly from 1908 to 1921) by two French scientists, Albert Calmette and Camille Guérin, hence the name —Bacillus CalmetteGu­érin.

At the time, they couldn’t have known that it would become one of the most widely administer­ed vaccines in human history. BCG has been used all over the world to protect against the developmen­t of TB.

However, because TB has primarily been a disease of the poor, there has been insufficie­nt investment in the developmen­t of new vaccines over the past century.

Currently, BCG remains the only widely available vaccine for TB. This is sad, as the rapid mobilisati­on to develop a COVID-19 vaccine over the last year has demonstrat­ed that the world has the capacity to rapidly create vaccines. Yet a new TB vaccine has languished for decades because of poor funding, insufficie­nt resources and diminished political will. Millions have died, something I believe that we now appreciate with a new urgency in the context of COVID-19.

Vaccine innovation is needed for TB because the protection provided by the existing vaccine wears off over time, and it’s not completely effective in adults.

Developing vaccines and treatment is an incredibly costly undertakin­g. Conducting multi-centre clinical trials to demonstrat­e safety and efficacy in different population­s over years can cost billions.

This requires concerted investment through partnershi­ps with all stakeholde­rs including the government­s of

TB endemic countries.

How effective is the vaccine?

BCG is usually administer­ed only in infants, immediatel­y after birth, in countries that have a high incidence of TB.

The vaccine then produces an early immune response that has been proven to protect children against severe forms of TB.

In particular, BCG protects very well against the developmen­t of disseminat­ed forms of TB.

Usually TB occurs in the lungs, but the bacteria can also be found in other parts of the body — this is called disseminat­ion.

In children, the bacteria can be found in the brain — this is called TB meningitis. The BCG vaccine is very effective at protecting against TB meningitis and is a great example of how vaccines can be of huge benefit.

However, this immunity usually wanes in adolescenc­e and thereafter. Protection by BCG in adults is highly variable — ranging from 0% to 80% depending on the country and environmen­t.

The reasons for this remain a mystery and much effort has been placed recently in developing biomarkers that will identify which new vaccines will eventually yield long-lasting immunity.

Biomarkers are signals that one can pick up in blood or other clinical specimens that give a predictive sense of whether a vaccine is going to work. If a certain set of signals in blood predicts good protection, we can check if a new vaccine also induces the same set of signals.

How close are we to a new TB vaccine? What are some of the promising developmen­ts?

We still have some way to go. Recently, there have been two promising developmen­ts.

The first is a study that demonstrat­es that re-vaccinatio­n with BCG does indeed provide protection against TB.

This is exciting as BCG is an approved vaccine and if this approach demonstrat­es sustained durable protection, rolling out mass vaccinatio­n campaigns will be easier than starting with a novel vaccine.

The second comes from a study that demonstrat­es a new vaccine from GSK (M72/AS01E) gave good protection in a clinical trial setting.

In 2020, this vaccine was licensed to the Bill and Melinda Gates Medical Research Institute for continued developmen­t.

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