There are two ways for the body to tackle infectious diseases - curing and prevention. Curing involves the use of drugs and other associated treatment modes. Prevention aims at stopping the entry and action of the infecting germ. Vaccination is a time-tested method of preventing germ-borne diseases. It involves allowing the body to recognise the presence of the cells and molecules of the invader (also called pathogen) and generate counter-molecules that capture and ‘karate chop’ it into submission and removal. Indeed, this strategy is stored and maintained in our body such that when the same pathogen strikes again (say in an epidemic), our defence is ready to strike and overcome it. The body has learnt to be immune to the invader. Our immune system is quite versatile and geared to defend itself, using proteins called immunoglobulins (also called antibodies) against a large variety of pathogens.
Vaccination involves injecting into the body a small amount of ‘sham’ (dead, i.e., usually heat-killed or highly disabled) pathogen, and allowing the body to generate the antibodies specific against the injected pathogen. This of course requires that we isolate and grow (‘culture’) the pathogen in the lab in order to inject it into the body. Happily enough, with many of the common infective diseases (e. g., measles, smallpox, polio, cholera, diarrhoea, hepatitis), this has been done, and we have successful vaccines against them. What if the disease pathogen is not easily cultured in the lab?
One such disease, which has been with us since antiquity, is leprosy. (The Mahabharata tells us that how Pratipa’s son Devapi could not ascend the throne of Hastinapur, since he had leprosy and instead retired to the forest for penance). Fortunately, most of us humans (about 99%) are able to resist infection by the leprosy-causing germ mycobacterium leprae, or M leprae. But the rest who succumb (majority of them in Asia and Africa), are shunned by society, have deformed limbs and prone to other infections, notably tuberculosis or TB. While drugs against leprosy exist, they are expensive, need repeated doses and not 100% effective. Vaccination would be the ideal solution.
It was this problem of generating a leprosy vaccine that Professor Gursaran Pran Talwar at the All India Institute of Medical Sciences (AIIMS) Delhi (a city 90 km southwest of Hastinapur) decided to address, way back in the early 1970s. But, the odds were very high indeed. M Leprae is not culturable; it simply does not grow in any medium. Hence to make a dead or attenuated pathogen for injection to generate antibodies was a challenge. In order to address this issue, Dr Talwar and his students combed through 16 different cultivable, atypical members of the mycobacterium family — distant relatives of M Leprae. Over the years, five of them appeared hopeful, and after almost two decades of work, one of them, termed mycobacterium w (simply called M w ) appeared to fit the bill.
Doppelganger
Note that M w is not M leprae, but what the Germans call a Doppelganger (or a double, an imitator). It was cultivable, it induced the molecule lepromin just as M leprae does, and thus was fit to be tried as a vaccine candidate. When tried on leprosy patients in Kolkata and Delhi, Mw generated lepromin responses and was also found to be quite effective.
Next, a detailed molecular and genetic analysis was carried out by Talwar and his students at the National Institute of Immunology (or NII, which Dr Talwar had founded, moving from AIIMS, in the early 1980s). Total characterisation of this microbe, and its genetic similarities to M leprae, and also to the TB pathogen M tuberculosis, were revealed by Syed Rahman, Seyed Hasnain and colleagues. It was further found that heat-killed M w can still boost immune responses against several pathogens. In honour of Dr. Talwar, who spearheaded the entire work, M w was renamed as mycobacterium indicus pranii, or simply as MIP. (The word indicus denotes India, while pranii comes from the middle name of Talwar and NII for the Institute).
Encouraged by the above trials, and clearances from the Drug Controller General of India and the US Food and Drug Administration, Dr. Soumya Swaminathan of Indian Council of Medical Research has announced that this vaccine will now be tried on people who are in close contact with leprosy patients in Bihar, Gujarat and Tamilnadu, and has said that MIP has the potential to bring down new cases of leprosy by 60% in three years.
We noted above that MIP shares some of its antigenic molecules with MTb. So, why not try it out as an anti-TB agent?
Doppelganger has more up its sleeve
They first infected one set of guineapigs with MTb and found that the animals had contacted the disease, as seen in their lungs and spleen. Next they first immunised another set of animals with MIP and then infected them with MTb. This reduced the pathology of the animals significantly. Encouraged by this, they next conducted an exploratory trial on hard-to-treat TB patients in Ahmedabad to find that those injected with MIP along with drugs had better results than control ones. There thus appear some similarities between MIP injection and the classical BCG vaccination we all have gone through against TB.
And most recently, Professor Dipankar Nandi of IISc Bengaluru has tried using MIP as an anti-cancer agent, since MIP appears to stimulate cells and molecules, such as IFN-gamma and IL-12, which play crucial riles in anti-tumour immunity. Now they have tried the combination of MIP along with the anti-cancer drug cyclophosphamide as a combination therapy with promising results (Podder et al, Clinical Cancer Drugs, 2016).
The Talwar saga bears testimony to what Louis Pasteur, a vaccine pioneer, once remarked: ‘where observation is concerned, chance favours the prepared mind’.
dbala@lvpei.org
