2002 — a boom year for vaccines!

The year 2002 has seen vaccines being developed for viral diseases such as HPV and HSV.

The year 2002 has seen vaccines being developed for viral diseases such as HPV and HSV.  

THE YEAR 2002 has been a great one for the vaccinologists. These are people who aim to develop vaccines against specific diseases that afflict humans and animals.

During the last 11 months alone, they have reported the invention of vaccines against nicotine (which should help people overcome the smoking habit), cocaine (to help kick addiction to this mind and body crippling drug), herpes simplex virus or HSV-2 (against the virus that causes warts, rash and blisters in the genital area), and human papilloma virus type 16 or HPV-16 (which is responsible for causing as much as 50 per cent of cervical cancer in women). There is also a glimmer of hope that a vaccine against the dreaded virus that causes AIDS may soon be available; trials of a HIV vaccine in humans are currently on.

It was but eight generations ago in the year 1798 that the British physician Edward Jenner developed the first vaccine. Intrigued by why some milkmaids contracted and suffered from the dangerous disease small pox while other milkmaids remained perfectly healthy, he invented the idea of injecting a small amount of the fluid containing what we now know as the cowpox virus into people to immunize them from smallpox.

Since the material came from cows, he termed the procedure vaccination (Vaccinus in Latin means `from cows'; Vacca refers to a cow). Thus was vaccinology born. It developed rapidly in the nineteenth century, particularly with the efforts of Louis Pasteur, the father of microbiology and later of Robert Koch. More recently in the 1960s and 1970s, a method to accurately fine tune vaccines was developed by Cesar Milstein and Georges Kohler. This method, called the production of monoclonal antibodies, allows us to pinpoint and selectively target a particular type of virus or a molecule. This specificity is important since a virus found in Europe is not necessarily identical to the one found in India.

The coats they wear or the shapes of their outer surface differ subtly, just as the shoes or the gloves of two non-identical twins do. The Milstein-Kohler method picks out this bit of difference and allows one to develop vaccines against local isolates of a germ. Incidentally, it is important to highlight a point of interest here and that is, neither Jenner, Pasteur nor Koch, Milstein or Kohler thought it right to claim exclusive ownership of their inventions. They did not protect their `intellectual property' through a patent, but let it be used freely by all for the welfare of humankind. I recall with admiration how simple both Milstein and Kohler were, and how easy to approach and interact with. They had come to Hyderabad several years ago to visit CCMB. Kohler borrowed a bicycle and took off on a tour of the old city all by himself and Milstein sat around the students in the CCMB cafeteria, enjoying the `rap sessions' and the local food, and telling them of his early years in Argentina and his life in England. We were deeply saddened to hear of their deaths (Kohler in 1994 and Milstein in 2002). In this boom year of vaccines, let us remember them with gratitude.

Within these eight generations, we have won against a dozen life-threatening diseases and thus extended the life span of humans on earth. As WHO has noted, the two most important measures of public health in the world have been safe drinking water and vaccination. Today we have effective vaccines against smallpox, rabies, plague, diphtheria, whooping cough, tuberculosis, tetanus, yellow fever, polio, measles, mumps, cholera, flu and hepatitis B. Thanks to vaccines, we have wiped out smallpox.

Plague is a thing of the past too and polio will become so in a few years. While a vaccine against leprosy has been developed in India, this scourge is essentially gone too thanks to drugs. While vaccines against cholera are available and more effective ones are being invented right here in India, this disease too is quite easily avoided just by handling sewerage waste effectively and by providing safe drinking water. It is a matter of shame that while our scientists are exhorted to work on cholera vaccine and are trying earnestly to do so, the Government has made no serious commitment to either making simple and safe latrines available, or planning on providing safe drinking water to the people. A country can be called developed only if one can open any tap there and drink the water out of it. While public health measures can effectively win over the threats of many of these diseases, vaccines need to be developed against several others. Notable among these are viral diseases such as HPV, HSV, and HIV. Good news about the first two has come just last month. A controlled trial on a human papilloma virus type 16 (HPV-16) vaccine has been published by Dr. Laura A. Koutsky of the University of Washington, Seattle and her associates in the November 21, 2002 issue of The New England Journal of Medicine (NEJM). HPV is sexually transmitted and is present in 50 per cent of cervical cancers in women. More than 4,50,000 cases of cervical cancer are diagnosed worldwide and over 2,50,000 women die of it each year. Screening for it is done using the Papanicolau test, called the Pap smear test, where the doctor scrapes away some cells from the cervix and tests them for abnormalities. This is a useful diagnostic procedure and the direct connection between it and the occurrence of cervical cancer is a subject of study (in which my own daughter Akhila, in Laura Koutsky's group, is engaged).

The development of the HPV vaccine had not been easy; it took more than a decade and a half. The problem is the extremely low number of virus particles that can be collected from the infected body. (Our immune system clears them well enough such that less than 10 per cent of the infected women actually develop cancer. Yet the above numbers indicate how prevalent HPV infection can be).

A breakthrough came about during 1991-93 by Zhou, Sun, Stenzel and Frazer of the papilloma research unit of the Princess Alexandra Hospital at Brisbane, Australia, who generated a vital component of the virus called L1 protein by genetic engineering methods, and built a virus-like particle using L1 alone. This particle is an empty nest. It looks and behaves just like the real virus but iit s harmless since it cannot proliferate, as it has no genetic material inside.

And this is what the immunologist wants, since the antibody he raises against it should work against HPV itself as the size, shape and the outer surface are all the same. This is precisely what happened, and a vaccine against the L1 particles was developed.

The drug firm Merck supported this endeavour, and supplied the Koutsky group with this vaccine, which they tried out on about 2200 women. The study went on for 3 years. The results, analysed using rigorous statistics, proved most rewarding. The vaccine is both curative and preventive — it not only prevents the disease from developing but also prevents the virus from staying in the body and passing on the infection.

This is great news indeed, and also relevant to the Indian scene. Professor Nirmal Ganguly of the Indian Council of Medical Research tells me that it is HPV-16 (and 18) that are seen in 96 per cent of Indian cases. The present vaccine (or its mild modification) should work well here.

Close on the heels of the HPV vaccine come the news of vaccines against HSV, nicotine and cocaine. In the same issue of NEJM, Drs. L. R. Stanberry and others report on a protein conjugate vaccine against genital herpes, which protects women.

Dr. N. Lindblom and colleagues at the Karolinska Institutet in Sweden have generated a monoclonal immunogen (a protein complex of nicotine) and shot rats with it. Two papers by them in the journal Respiration earlier this year indicate that such vaccination abolished the craving for nicotine, and also the `reward' or `kick' that nicotine offers the animals.

If such a vaccine works with humans, it can be used for both quitting smoking as well as against starting it in the first place. And a vaccine against cocaine has been in the development for the last five years. The results of a human trial, reported in the January 2002 issue of Vaccine, are very promising.

Finally, some exciting news from Bangalore. Drs. P. N. Rangarajan and G. Padmanaban of the IISc have developed a DNA-based vaccine against rabies. Why DNA and not the usual protein base? Because, they rightly argue, DNA is more robust and less demanding; it is easier prepared, is cheaper and does not need to be transported in a `cold chain'. This DNA vaccine is currently used as a component in the conventional rabies vaccine and the trials have been very encouraging. These Bangalore scientists believe that the use of DNA may well be a viable future trend in vaccinology.

D. Balasubramanian

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