Vaccines and vaccination / by Gordon L. Ada

Vaccines and vaccination by Gordon L. Ada Professor Gordon L. Ada is visiting Professor at Johns Hopkins University, USA I n ancient times , it was observed that those who survived an in-fectious disease seldom suffered a second , similar sickness; and this was particularly apparent in the case of a disease like smallpox which left characteristic pockmarks on the skin. Sometimes a mild in- fection could be related to the site of the disease symptoms , and this led to the practice of deliberate in- fection with the disease agent at these sites-a hazardous procedure. The first demonstrably safe pro- cedure for preventing infection -the process now called vaccina- tion- was carried out in 1796 by Edward Jenner. He inoculated a boy with infectious material from cows (cowpox virus) and then showed that he was immune from smallpox by injecting him with ma- terial from a victim's smallpox scab! Louis Pasteur later developed (initially by chance) the means of changing the properties of microbes so that their potential for causing disease (a property called viru- Lence) was much reduced without greatly affecting their ability to in- duce an immune response. This process of attenuation was subse- quently used to develop some of our most successful vaccines, par- ticularly to control diseases caused by viruses. Viruses and many bacteria cause disease by damaging or killing the cells they infect; consequently, a vaccine aims to prevent infection of these cells by the virus or bacteri- um. Many vaccines consist of the live , attenuated organism; or, if such a preparation is either not available, or cannot be made, the virus or bacteria is inactivated (killed) before being administered. Other bacteria secrete powerful poisons which damage the host's cells, so protection against these bacteria called for a different strat- egy. The isolated poison was made W ORLD HEALTH , July 1988 the basis of the vaccine but it had to be inactivated in a special way be- fore it could be safely administered. The six vaccines against the com- mon childhood diseases which form the basis fo WHO's Expanded Pro- gramme on Immunization are pre- pared by one or other of these three procedures : the measles and polio vaccines are attenuated strains of these viruses , and an inac- tivated preparation of polio virus is also available; BCG against tuber- culosis is an attenuated form of the tubercle bacillus; the pertussis vac- cine is an inactivated preparation of the bacteria that cause whooping cough; the diphtheria and tetanus vaccines are composed of the inac- tivated poisons (toxins converted to toxoids) secreted by those bacteria. Cowpox sores on a milkmaid's hands inspired Dr Edward Jenner to develop the vaccine that eventu- ally eradicated smallpox. Photo WHO There are about 50 vaccines for human use currently approved or under trial. With few exceptions, they are for the control of viral or bacterial diseases , and those in common use vary in their efficacy. The live attenuated viral vaccines are generally the most effective. World-wide use of the smallpox vaccine, based on vaccinia virus (vacca is the Latin for a cow) and progressively developed since Jen- ner's day, achieved the ultimate goal of a vaccination programme- the eradication of the disease itself. Measles, rubella (" German mea- sles"), yellow fever and polio vac- cines can give life-long protection from these diseases. Though vac- cine administration may cause some side-effects, a comparison of the incidence of complications fol- lowing infection with the wild-type measles virus versus the vaccine dramatically demonstrates the ad- vantage of vaccination. In the Uni- ted States, immunization of chil- dren with measles vaccine prior to school entry is now required by law, with the result that indigenous measles has virtually disappeared from that country. Though widely used, BCG has given variable re- sults . It has proved to be an effec- tive vaccine for infants but has giv- en variable results in adults . A trial of this vaccine in South India showed such poor protection against tuberculosis that , because of the continuing global importance of this disease, it was clear that we needed more detailed knowledge of the biology of the bacterium and of the immune responses that would give immunity from infection. This led to the establishment , in 1984, of the WHO Vaccine Development Pro- gramme which supports research on a number of viral and bacterial diseases for which new or improved vaccines are needed. These vaccines have reduced the burden of infectious disease to a much greater extent in developed than in developing countries , partly because of wider coverage of the population in the former but also because the other infections are much more prevalent in the latter countries. The wHo Programme on Tropical Diseases Research (TDR) was established to support research aimed at controlling one bacterial (leprosy) and five parasitic diseases prevalent in these countries. At present, a vaccine to control lepro- sy and several preparations aimed 5 at different stages of the life-cycle of the malaria parasite are under trial. Similarly, WHO's Diarrhoea! Diseases Control Programme (CDD) aims to develop means of controlling diseases of the gastro- intestinal tract , while new vaccines to control rotaviral infections , which cause serious diarrhoea in in- fants, and cholera are being tested. The need for these and other vac- cines is great. A third of the world's population is at risk of malaria infection and millions suffer from simultaneous infection by several parasites. The appearance of AIDS due to infection by the human im- munodeficiency virus, HIV , is al- ready of major concern in devel- oped countries but seems certain to have devastating consequences in some developing countries. What can the new knowledge of immuno- logical processes and the new tech- niques of the molecular biologists contribute to making effective vac- cines to control these diseases? Serious reaction following Broadly speaking, there are two main new approaches towards vac- cine development. The first at- tempts a synthetic approach by making in the test tube those parts of the virus or bacteria or parasite which are thought to be the most important for stimulating the im- mune response. The synthetic pre- paration, composed of peptides, should provide an entirely safe vac- cine, by contrast with existing vac- cines which may cause side-effects, sometimes serious, in a very small proportion of recipients . However, the as-yet-unresolved question is: will such vaccines be as effective in preventing disease as the con- ventional approach? If used by themselves , the answer is No! They must be combined with other molecules and administered with an adjuvant (a preparation which enhances the immune response to the peptide). The second approach is to use techniques which involve isolating For every 100,000 cases Measles Pneumonia Convulsions Brain damage Early death infection 5,000 720 280 10 Measles ' vaccination 1 60 0.1 0.02 6 Above : To remain potent vaccines must be kept cold: in a hospital in Thailand, a user's guide is printed on the refrigerator. Photo WHO/Zafar Left : At a research centre on influenza in the United Kingdom, nasal washings are obtained from patients in order to isolate viruses. Photo WHO/D. Henrioud Far right: There are about 50 vaccines for human use; bacterial vaccines are produced by fermenting bacteria in these huge vats. Photo Swiss Serum and Vaccine Institute © the DNA coding for antigens , transforming cells with the DNA so that the antigen is now produced by these cells and can be used as a vac- cine . A variation of this approach is to incorporate this DNA into an ex- isting vaccine , such as the smallpox vaccine , so that this well-tried vac- cine can be used to protect against another disease, such as malaria. The smallpox vaccine did however cause side-effects , with occasional deaths. Fortunately, novel ways of making such a " hybrid vaccine" both more safe and more effective than the parent vaccine have re- cently been described , but such preparations have yet to be licensed for human use. There have also been advances in developing oral vaccines. A "gene- tically-disabled " form of a Salmo- nella organism, which can be taken orally , has been successfully used to protect against typhoid fever in tri- als in Egypt. DNA coding for an important antigen of the organism causing cholera has been incorpo- rated into this Salmonella , and tri- als are in progress to establish whether this hybrid vaccine will now also give protection against cholera. If so, it can readily be ap- preciated that such hybrid vaccines offer the possibility of developing multivalent vaccines . In other words, WORLD HEALTH, July 1988 Vaccines and vaccination some day a single vaccine may pro- tect against several diseases- a pre- cious boon in tropical countries where there is so much infectious disease. Scientists working in these areas are justifiably confident that apply- ing these new approaches should lead to the development of vaccines against many diseases, particularly such parasitic diseases as malaria . But the future is not entirely rosy. Infectious micro-organisms have eo-evolved with man over millen- nia , and the " cleverest " micro-or- ganisms have developed means of by-passing man's defences so that they continue to survive and to plague us. One example i.s the influ- enza virus. By continually changing its properties , this virus escapes pre-existing antibodies and infects susceptible cells. This is why the currently available vaccines are only partially successful. The virus can be controlled at a later stage, but not before it has caused the Or Barry Bloom, in his Presidential Address to the American Associa- tion of Immunologists in 1986, pre- sented a graphic summary of the situation in tropical and other developing countries. "This is the Third World, in w hich 75 per cent of the planet's population lives, where 86 per cent of all children are born and 98 per cent of all infant and child deaths occur, and where 10 kids die of vaccine-preventable illness every minute." symptoms of influenza and has spread to other people. It is the " perfect " virus; most people easily survive an attack and the virus con- tinues to flourish! In the process of adapting to hu- man hosts, HIV is still a major kill- er and, unfortunately, it seems to have nearly all the cards on its side. As well as the trick of changing its properties , like the influenza virus, it infects and destroys those cells which are an essential part of the immune system. For these reasons , it is difficult to develop a vaccine which would protect those at risk from infection by this virus. Our hopes for controlling AIDS rest on educating people about transmis- sion of the virus, and on the not un- realistic hope that an effective drug to control the infection will speedily be developed . • WORLD HEALTH, July 1988