Public Health (1991), 105, 273-275
© The Society of Public Health, 1991
Editorial
Aids Vaccines Currently it is estimated that over 1 million people in the U S A alone are infected with the H u m a n Immunodeficiency Virus (HIV). Acquired Immunodeficiency Syndrome (AIDS), which develops several years after H I V infection, was first recognised in 1981. Tests on stored samples of blood show the virus has been infecting humans since at least the early 1960s. World-wide, 314,611 cases of A I D S had been reported to the World Health Organisation by the end o f 1990. Estimates vary, but even if one calculates only ten cases of H I V infection for each case of A I D S , then a horrendous total o f over 3 million cases o f H I V infection world-wide is arrived at. The first wave o f the epidemic was a m o n g homosexual men, the second amongst intravenous drug abusers, a third is now starting a m o n g s t the heterosexual population, which is already the single biggest infected group in Third World countries, particularly in Africa. This has led not only to massive research into the development o f an A I D S vaccine, but also to research into drugs which will destroy the virus after it has invaded the body. F o r the sake o f m a n k i n d ' s future it is essential that the exponential increase in the n u m b e r o f cases o f H I V world-wide is halted. One o f the great success stories o f medicine is vaccination. Smallpox has been eradicated world-wide, other viral diseases such as poliomyelitis, measles and rubella are m o r e or less controlled, as are the bacterial diseases diphtheria and tetanus. Most o f the vaccines which are used are usually prepared by attenuation or inactivation o f the organisms which themselves cause the disease. However, for diphtheria and tetanus, inactivated proteins secreted by the bacteria themselves are used. In some cases--early forms o f rabies vaccine for e x a m p l e - - s e r i o u s side-effects m a y occur. In other cases, due to the variable nature of the antigen such as the c o m m o n cold virus, no effective vaccine is currently available. The production o f a successful vaccine can prove complicated, in addition to being both difficult and costly. There are p r o b a b l y at least 50 laboratories round the world where researchers are working on the development of an A I D S vaccine. M a n y different types of A I D S vaccine are being developed and the first team to succeed will reap fame, fortune and p r o b a b l y a Nobel prize. Already the search for an effective vaccine has been narrowed d o w n to several options, the aim being to p r o v o k e the body into mounting an immune response that blocks HIV. A successful vaccine must preferably stop the virus before it can infect a single cell. Hopefully drugs will be developed which will prevent the virus multiplying within body ceils or, better still, kill the virus. There are four major ways currently being studied to stimulate immunity to HIV. First by the use o f whole killed virus. The H I V is killed and then injected into the body in an effort to trigger antibody production without causing H I V infection. Tests on monkeys have shown that, under ideal conditions, the killed virus vaccine blocked infection by the m o n k e y f o r m o f HIV. A danger is that any improperly prepared vaccine m a y infect the person with H I V instead of protecting them. Because of its very nature, this type of vaccine carries a greater risk of causing infection with H I V than the following three types. A second vaccine can be prepared by genetic engineering. The H I V is altered by this process, just enough to m a k e it incapable o f causing infection, but it is still capable of stimulating the production o f antibodies. The potential for error is tremendous as this
274
Editorial
method has the potential of giving a lethal infection. Due to this, it is dangerous to test the vaccine in humans. The third method also involves genetic engineering. A genetically engineered protein that closely resembles the protein in H I V is produced. A vaccine made from this protein has been shown in experiments to protect chimpanzees against H I V infection. This variation does not have the same potentially lethal outcome as either of the previous vaccines. The fourth method is to use a restructuring o f the vaccinia virus. This vaccine also involves genetic engineering as the vaccinia virus is subtly altered to resemble HIV. Early studies in healthy h u m a n s have shown the vaccine is safe and it does stimulate some antibody production, but that does not prove it confers complete immunity to HIV. Inadequate protection might be worse than no protection, as it might give a false sense of security. Development of a vaccine is one thing, but carrying out trials on humans is fraught with difficulty. If a trial should go badly wrong the adverse publicity could stop the possibility of other trials for years. The cost in h u m a n suffering would be incalculable, particularly if at the same time adequate drugs for treating A I D S had still not been developed. In any trial, several thousand people at high risk of the disease would be given the experimental vaccine. The subjects in the trial would be monitored to see if they had a better record of avoiding infection than persons in similar 'at risk' groups who had not been vaccinated. In developed countries, for vaccine trial purposes, who would constitute the groups at high risk? Drug abusers and prostitutes are two groups at great risk, but they would be unlikely to co-operate in a vaccine trial. Because the antibodies generated by a vaccine would be the same as those found in H I V positive persons, all persons who might be used in the trial would have to cope with being labelled H I V positive. Due to all the problems which that label brings in obtaining insurance etc., groups which have sometimes been used in the past in drug trials such as students, military personnel, prisoners etc. might well refuse to co-operate. Alternatively, if vaccine trials are conducted in Third World countries, is that ethically acceptable? Persons in those countries have quite a different view o f Western medicine and m a y not fully comprehend the fact that it is an experimental vaccine and not guaranteed to protect against H I V infection. A further disturbing feature is commercial secrecy. Companies financing research naturally wish to achieve the m a x i m u m return on their investment. They are therefore loath to take part in comparison trials with other vaccines or to pool their research resources with rival companies. Because of the potential of being sued for causing infection in rare instances, commercial companies prefer to research genetically engineered vaccines rather than killed vaccines. T o c o m b a t this liability the US National Academy o f Sciences has urged the American Congress to pass a law to protect vaccine manufacturers against claims of this type. Other countries should follow suit and pass similar laws. The final problem is the cost of the vaccine when on sale in the market-place. A good example of what m a y occur is to study the Hepatitis B vaccine story. Hepatitis B is, like AIDS, a viral disease, which can be spread sexually or by contaminated blood or blood products. When the first vaccine was produced a b o u t nine years ago it cost over £60 per dose. A few years later, when a second manufacturer's vaccine was licensed for use in the U K , the price halved but it is still over £30 per dose. It is (unlike poliomyelitis vaccine) not yet freely available under the National Health Service in this country to absolutely everyone. The position in Third World countries is far worse even though, in m a n y o f them in the Far East, a r o u n d 30% of the population are infected with Hepatitis B.
Editorial
275
A successful A I D S vaccine will be hailed as one of the greatest benefits mankind has ever achieved, but will the same thing happen as with Hepatitis B vaccine? Will the A I D S vaccine be priced out o f the market except for certain listed groups in developed countries? Will the very countries where trials of new vaccines have been carried out be unable to benefit from a successful vaccine due to its cost? The World Health Organisation should be alerting all its members now to the fact that, when a successful vaccine is available, all countries must make adequate funds available for its administration. Vaccine manufacturers likewise must not seek to profit from the uniqueness o f their product because of its lifesaving potential. They must ensure there are no possible victims w h o m their product fails to reach simply because it costs too much. H I V infection is the m a j o r public health problem at the end of the 20th century. Let us hope it is conquered before the 21st commences. James M. D u n l o p
© The Society of Public Health, 1991
Editorial
Aids Vaccines Currently it is estimated that over 1 million people in the U S A alone are infected with the H u m a n Immunodeficiency Virus (HIV). Acquired Immunodeficiency Syndrome (AIDS), which develops several years after H I V infection, was first recognised in 1981. Tests on stored samples of blood show the virus has been infecting humans since at least the early 1960s. World-wide, 314,611 cases of A I D S had been reported to the World Health Organisation by the end o f 1990. Estimates vary, but even if one calculates only ten cases of H I V infection for each case of A I D S , then a horrendous total o f over 3 million cases o f H I V infection world-wide is arrived at. The first wave o f the epidemic was a m o n g homosexual men, the second amongst intravenous drug abusers, a third is now starting a m o n g s t the heterosexual population, which is already the single biggest infected group in Third World countries, particularly in Africa. This has led not only to massive research into the development o f an A I D S vaccine, but also to research into drugs which will destroy the virus after it has invaded the body. F o r the sake o f m a n k i n d ' s future it is essential that the exponential increase in the n u m b e r o f cases o f H I V world-wide is halted. One o f the great success stories o f medicine is vaccination. Smallpox has been eradicated world-wide, other viral diseases such as poliomyelitis, measles and rubella are m o r e or less controlled, as are the bacterial diseases diphtheria and tetanus. Most o f the vaccines which are used are usually prepared by attenuation or inactivation o f the organisms which themselves cause the disease. However, for diphtheria and tetanus, inactivated proteins secreted by the bacteria themselves are used. In some cases--early forms o f rabies vaccine for e x a m p l e - - s e r i o u s side-effects m a y occur. In other cases, due to the variable nature of the antigen such as the c o m m o n cold virus, no effective vaccine is currently available. The production o f a successful vaccine can prove complicated, in addition to being both difficult and costly. There are p r o b a b l y at least 50 laboratories round the world where researchers are working on the development of an A I D S vaccine. M a n y different types of A I D S vaccine are being developed and the first team to succeed will reap fame, fortune and p r o b a b l y a Nobel prize. Already the search for an effective vaccine has been narrowed d o w n to several options, the aim being to p r o v o k e the body into mounting an immune response that blocks HIV. A successful vaccine must preferably stop the virus before it can infect a single cell. Hopefully drugs will be developed which will prevent the virus multiplying within body ceils or, better still, kill the virus. There are four major ways currently being studied to stimulate immunity to HIV. First by the use o f whole killed virus. The H I V is killed and then injected into the body in an effort to trigger antibody production without causing H I V infection. Tests on monkeys have shown that, under ideal conditions, the killed virus vaccine blocked infection by the m o n k e y f o r m o f HIV. A danger is that any improperly prepared vaccine m a y infect the person with H I V instead of protecting them. Because of its very nature, this type of vaccine carries a greater risk of causing infection with H I V than the following three types. A second vaccine can be prepared by genetic engineering. The H I V is altered by this process, just enough to m a k e it incapable o f causing infection, but it is still capable of stimulating the production o f antibodies. The potential for error is tremendous as this
274
Editorial
method has the potential of giving a lethal infection. Due to this, it is dangerous to test the vaccine in humans. The third method also involves genetic engineering. A genetically engineered protein that closely resembles the protein in H I V is produced. A vaccine made from this protein has been shown in experiments to protect chimpanzees against H I V infection. This variation does not have the same potentially lethal outcome as either of the previous vaccines. The fourth method is to use a restructuring o f the vaccinia virus. This vaccine also involves genetic engineering as the vaccinia virus is subtly altered to resemble HIV. Early studies in healthy h u m a n s have shown the vaccine is safe and it does stimulate some antibody production, but that does not prove it confers complete immunity to HIV. Inadequate protection might be worse than no protection, as it might give a false sense of security. Development of a vaccine is one thing, but carrying out trials on humans is fraught with difficulty. If a trial should go badly wrong the adverse publicity could stop the possibility of other trials for years. The cost in h u m a n suffering would be incalculable, particularly if at the same time adequate drugs for treating A I D S had still not been developed. In any trial, several thousand people at high risk of the disease would be given the experimental vaccine. The subjects in the trial would be monitored to see if they had a better record of avoiding infection than persons in similar 'at risk' groups who had not been vaccinated. In developed countries, for vaccine trial purposes, who would constitute the groups at high risk? Drug abusers and prostitutes are two groups at great risk, but they would be unlikely to co-operate in a vaccine trial. Because the antibodies generated by a vaccine would be the same as those found in H I V positive persons, all persons who might be used in the trial would have to cope with being labelled H I V positive. Due to all the problems which that label brings in obtaining insurance etc., groups which have sometimes been used in the past in drug trials such as students, military personnel, prisoners etc. might well refuse to co-operate. Alternatively, if vaccine trials are conducted in Third World countries, is that ethically acceptable? Persons in those countries have quite a different view o f Western medicine and m a y not fully comprehend the fact that it is an experimental vaccine and not guaranteed to protect against H I V infection. A further disturbing feature is commercial secrecy. Companies financing research naturally wish to achieve the m a x i m u m return on their investment. They are therefore loath to take part in comparison trials with other vaccines or to pool their research resources with rival companies. Because of the potential of being sued for causing infection in rare instances, commercial companies prefer to research genetically engineered vaccines rather than killed vaccines. T o c o m b a t this liability the US National Academy o f Sciences has urged the American Congress to pass a law to protect vaccine manufacturers against claims of this type. Other countries should follow suit and pass similar laws. The final problem is the cost of the vaccine when on sale in the market-place. A good example of what m a y occur is to study the Hepatitis B vaccine story. Hepatitis B is, like AIDS, a viral disease, which can be spread sexually or by contaminated blood or blood products. When the first vaccine was produced a b o u t nine years ago it cost over £60 per dose. A few years later, when a second manufacturer's vaccine was licensed for use in the U K , the price halved but it is still over £30 per dose. It is (unlike poliomyelitis vaccine) not yet freely available under the National Health Service in this country to absolutely everyone. The position in Third World countries is far worse even though, in m a n y o f them in the Far East, a r o u n d 30% of the population are infected with Hepatitis B.
Editorial
275
A successful A I D S vaccine will be hailed as one of the greatest benefits mankind has ever achieved, but will the same thing happen as with Hepatitis B vaccine? Will the A I D S vaccine be priced out o f the market except for certain listed groups in developed countries? Will the very countries where trials of new vaccines have been carried out be unable to benefit from a successful vaccine due to its cost? The World Health Organisation should be alerting all its members now to the fact that, when a successful vaccine is available, all countries must make adequate funds available for its administration. Vaccine manufacturers likewise must not seek to profit from the uniqueness o f their product because of its lifesaving potential. They must ensure there are no possible victims w h o m their product fails to reach simply because it costs too much. H I V infection is the m a j o r public health problem at the end of the 20th century. Let us hope it is conquered before the 21st commences. James M. D u n l o p
