A ‘pain-free’ vaccine for TB

Nobody likes needles. Especially when ‘the jab’ doesn’t come with an assurance that it will actually work. This is just one of the struggles faced by Tuberculosis health care officials around the world, but collaborative research from the Malaghan Institute and Otago’s Immune Solutions Ltd - published today in the scientific journal PLoS ONE - suggests a solution could be at hand.

Tuberculosis (TB) kills more people worldwide than any other bacterial disease, with one third of the world’s population currently infected with Mycobacterium tuberculosis. In New Zealand there are about 600 notifications of the disease each year, with 300 new cases diagnosed.

The bacteria that cause TB attack the lungs, leading to a persistent cough, night sweats, and weight loss. The disease is spread through the air when an infected individual coughs or sneezes, and is more prevalent in conditions of household crowding and relative poverty.

“Bacille Camette-Guerin (BCG) is the only available vaccine for the prevention of TB and has been given to over three billion individuals, making it the most widely administered vaccine to date,” says Malaghan Institute TB researcher Lindsay Ancelet. “The problem is, it doesn’t work in everyone.”

BCG is a live bacterial vaccine that is typically given soon after birth. While it is effective at preventing TB during childhood, its effectiveness wanes over time. In fact the efficacy of BCG against adult TB disease can range anywhere from 0 to 80%.

Despite this, BCG’s proven safety record and its success in reducing childhood TB makes it a good starting point for developing more effective TB vaccines.

One strategy for improving the effectiveness of BCG is to change the way in which it is administered – something Lindsay has been investigating as part of her PhD research under the supervision of Dr Joanna Kirman.

“Oral delivery of BCG has many advantages over the standard ‘skin jab’ method of BCG vaccination, including reduced cost, ease of administration, avoidance of needles and the associated risk of disease transfer,” says Lindsay.

“More importantly, it has been shown that oral delivery more effectively targets the mucosal immune response. This is critical, given that the primary site of TB infection is the lungs.”

For the oral vaccine to work, the bacteria need to be alive. Dr Frank Aldwell and colleagues from Immune Solutions Ltd have developed a lipid formulation called Liporale^TM that coats the BCG bacteria, allowing them to survive the harsh environment of the stomach.

“In our PLoS ONE research we demonstrated that oral delivery of Liporale^TM-BCG stimulated an immune response in the lungs of mice that was superior to that achieved by injecting BCG,” says Lindsay. “What’s more, the immune response in the lung was long lived. This is important because it can be many years until re-encounter with the pathogen that causes TB.”

The lung is the site of TB infection, so any improvement to the immune response elicited here by the BCG vaccine is more likely to provide long-lived protection against TB disease.

Earlier this year, Lindsay and Dr Aldwell presented the team’s findings to AERAS – a US-based Bill and Melinda Gates-funded not-for-profit organisation that supports the development of novel, superior TB vaccines – who are interested in taking this new vaccine further.

Publication details:

Ancelet LR, Aldwell FE, Rich FJ, Kirman JR. (2012) Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4+ T cell memory immune response. PLoS ONE (in press)

Enquiries

Please contact Lindsay Ancelet on +64 4 499 6914 or [email protected]

Funding:

Dr Joanna Kirman was a Malaghan Haematology Fellow of the Wellington Medical Research Foundation.

Additional note:

This collaborative research was undertaken at the Malaghan Institute over the last couple of years by PhD student Lindsay Ancelet under the supervision of Dr Joanna Kirman.  In May of this year, Dr Kirman relocated her research programme to the University of Otago, where this work will continue.  Lindsay is still based at the Malaghan Institute, currently writing up her PhD thesis.

Image caption: Infectious Diseases PhD student Lindsay Ancelet