Of vaccines of promise

Print edition : April 14, 2001
Interview with Dr. Hans Wigzell.

"The global trend is towards application-oriented research. This... would kill curiosity-driven research, the basis of several crucial discoveries," says Prof. Hans Wigzell, Rector and Professor of Immunology, Karolinska Institute, Sweden.

A specialist on vaccines, Prof. Wigzell chairs various international AIDS vaccine initiatives such as the World Health Organisation's HIV vaccine committee and the International AIDS vaccine initiative, as also the European vaccine committee.

In Chennai recently to participate in an international congress on immunology, the chairman of the Nobel Assembly and the Committee for the Nobel Prize for Medicine and Physiology spoke to Asha Krishnakumar on various vaccine trials that are on, the cost of vaccines and the role of governments in reaching vaccines to all. Excerpts from the interview:

Has there been a blurring of distinction between basic and applied sciences in immunology and vaccine development?

K. GAJENDRAN

The global trend now is towards application-oriented medical experiments. This is primarily because many of those who finance medical research are concerned about its application - more than ever before. This could be dangerous from the point of view of curiosity-driven medical research. But this is the reality today.

The National Institutes of Health, which is the major funding agency in the United States, is politically under the Department of Health. Thus, all medical research is health-driven. Europe also has a clear bias towards application. In Sweden, the large institutions, including the Strategic Research Foundation, which has invested $ 3 billion, are heavily tilted towards application.

Thus, molecular biology research is moving towards developing new products, proteins, antibodies and the like. Also, an analysis of the basic genome structure of the micro-organism provides for the development of products for various bacterial diseases. A lot of research is also on for the production of antibiotics and vaccines. There is a movement towards applied science. Never before has there been so many clinical trials in vaccines.

On the other hand, there is also a movement in the universities to defend curiosity-driven research which, I think, should have its space. For many of the inventions which do not have immediate commercial consequences but are good for human beings in the long-run would not have been possible had research been confined to application. As a majority of the patents come from university research, these establishments are spearheading the movement towards curiosity-driven research.

Some of the big pharmaceutical companies, such as SmithKline Beecham, American Home Products, Wellcome, Glaxo and so on, which abandoned vaccine research 10 years ago, are getting into it once again because they see it as becoming profitable. They are involved in various trials - for making better vaccines against classical diseases such as tuberculosis and malaria, new vaccines against old diseases such as meningitis and also against new viruses like HIV, the human immunodeficiency virus.

Trials and molecular biology research going on simultaneously all over the world have given new insights into many diseases. For example, diseases such as cancer are now found to be 'approachable' by vaccines. With developments in molecular research and diagnostic techniques, it is now possible to understand why a particular tumour in a particular individual has a particular molecule. This can be targeted during treatment.

Thus, trials on various vaccine approaches are on around the world, with some positive reports here and there. It would be naive, however, to believe that a major breakthrough is round the corner. It will only be a gradual development.

What are the promising vaccine trials? And how far away are scientists from the development of vaccines for slow onset diseases?

Development of vaccines against many infectious diseases shows a lot of promise. Developing a vaccine against HIV, in which I am also involved as chairman of the WHO HIV Vaccine Committee, is a tough job. But you may probably have a vaccine against HIV in a few years. You can make human antibodies against HIV. There is a biological feasibility, though right now the frequency of success in inducing that kind of an antibody is way too low.

Work on auto-immune diseases is going on, but it is very tricky because we do not yet know whether the self-destructive mechanism is a cause or the consequence.

Thus, a number of promising vaccine approaches are being tried. But it is hard to predict how many, and if at all, would have a clinical consequence.

Some areas in which trials are going on vigorously include antibodies against hormones, and vaccines against contraception and arteriosclerosis. The most exciting research is on for a vaccine against Alzheimer's disease. The mice-model shows positive results. It shows that some kind of protein gets precipitated in the brain and if you vaccinate against cell protein, antibodies block the precipitation and even if the damage has started it clears. The clinical trials of this protocol are now in the second phase. This is predicted to be a fantastic discovery. If it functions for Alzheimer's then there is a lot of hope for other brain diseases.

What are the vaccine trials going on against major slow-onset diseases such as HIV and diabetes?

In the case of HIV, the WHO selected four countries - Uganda, Rwanda, Thailand and Brazil - for vaccine trials. In Thailand, the GP 120 (based on glycoprotein) trial against HIV is on. My guess from the trial data is that it would be a weak vaccine - it could give, maybe, 10 to 15 per cent protection.

Some interesting trials are on in Africa. For instance, in Kenya, there is a trial using "vaccinia virus" (small pox). Some genes of HIV are introduced in this virus and used for vaccination. Some intelligent vaccines are developed using this method. Pieces of HIV genome are taken and certain protein parts which are known to provoke aggressive cell-mediated immunes are expressed in it. Subsequently they are given a booster with the protein. The booster is usually GP 120, 140 or 160.

In South Africa, a virus vector is used with an HIV gene-construct. This is also a trial that raises much hope.

Thus, at least four different Phase I trials for HIV are going on in Africa. Some early trials are on in the U.S. But one in the U.S. and another in Thailand have reached Phase III and some results can be expected in a year or two. But these are the weak vaccines. Others - stronger ones - may take longer. Thus it is naive to believe that we can get any striking positive data on HIV vaccines in a couple of years.

A large number of trials are done for malaria, mostly using DNA vaccines. The U.S. Navy has taken up a major effort in this.

What I would like to see is a vaccine against nicotine. Very interesting research is going on in this area by attaching the nicotine molecules to a carrier protein and making antibodies. This has proved to be very good in animal trials. When vaccinated with this, the animals wean themselves from nicotine. There would be clinical trials for this soon.

Will the results from the human genome project help in vaccine development?

In medicine, an understanding of the complex human metabolism is very helpful. So, the human genome project should provide us with some rich information. For example, it would provide us with a lot of insights into the side-effects of drugs and the administering of correct dosages of medicine. It would help greatly in vaccine development against auto-immune diseases as we would now be able to understand the immune systems better.

There is a controversy in the U.S. and also in Europe about the Hepatitis B vaccine causing autism in children. Is there any scientific basis for this fear?

The allegation is crazy. Public concerns are largely because the media are projecting, falsely, that some vaccines are causing complications. Some reports say that mental disturbances are caused by the vaccine against whooping cough, autism by the Hepatitis B vaccine, allergies by some others, and so on. But if you look at all the data from the commonly accepted vaccines, none other than oral polio has any negative effect. The oral polio vaccine can rapidly mutate to become aggressive. This may happen in one in 100,000 cases or so. This is proved scientifically now. But none of the other allegations are true.

The triple vaccine MMR - against measles, mumps and rubella - was said to cause meningitis. But when we did a survey we found that in over one million children only 34 got meningitis. And that was also not because of the vaccine. In fact, it was found that the vaccine protected children from meningitis. So, the allegation was absolutely baseless.

These vaccines when developed and marketed are very expensive, particularly in developing countries where it is needed most. What institutional or structural changes are needed to make them cheaper?

It is a shame if the vaccines are not used among a large section of the population. But the prices of many of the older vaccines have come down drastically. To address the problem of costs, governments must play a proactive role. They should spend on vaccine research. I am disturbed by the military expenditure of some of the countries. A major responsibility rests with the political leadership. Poorer countries should devise a sound drug pricing policy, one that ensures basic medicines and vaccines for all. Cost of the vaccine is not a problem, but the attitude of our leaders is.

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