- Email: [email protected]
Vaccines at ‘Microbe 86’
Conference Report Vaccines at 'Microbe 86' September 1986, Manchester, UK In the spring of the year 1886 the French Academy of Sciences appointed a commission who established a fund to finance the construction of the Institute Pasteur in recognition of the Pasteur's demonstration of the efficacy of the post exposure rabies vaccine prepared from rabbit nervous tissue. Two and a half years later the President of the French Republic opened the new laboratory. One hundred years have passed since those heady days. Vaccines have already played a major role in controlling those microorganisms which were the dread and magic causes of disease and widespread death. What then, did those who have chosen to walk in Pasteur's footsteps occupy themselves with during their week of congress in Manchester in September 1986? During the one and a half days devoted to vaccines, delegates were offered some 16 verbal presentations and 35 posters. Two thirds of the offerings described materials or methods for the generation of bacterial prophylactics while the remainder focussed on viruses. Indeed the mood of the bacterial presentations was marked by an excitement at the progress which was being made in the use of the new understanding of the molecular structures at the periphery of the gram negative bacteria and the discovery of the groups of either chromosomal or plasmid borne genes which coded for such molecules. The value of the work was well recognised for two reasons. Firstly, many of the bacterial diseases are caused by a large number of closely related yet immunologically distinct subtypes, which implies that the development of a vaccine which is capable of inducing protection against such a plethora of organisms would be a significant and important achievement. Secondly, the evolution of composite plasmids expressing genes which confer on their possessors the ability to withstand the bactericidal or bacteriostatic effects of the commonly used antibiotics requires that the scientific and technological community should reconsider the need for the development of vaccines against those bacterial diseases which have in recent times been held in check by the use of anitbiotics.
By way of contrast, the papers presented in the virus vaccine session lacked the edge that was evident in the bacterial presentations. It is clear that the simpler structure of viruses has led to complete three-dimensional descriptions at the atomic level for the small icosohedral particles of poliovirus and rhinovirus. Such knowledge is at present being exploited by those who wish to develop new subunit vaccines for the diseases mentioned and also for foot-and-mouth disease. The hypothesis that such a detailed knowledge of the structure of the virus would lead to a new generation of 'scientific vaccines' is clearly under test at this time. It could be that knowledge of the structure of the infectious particle is insufficient and that the 'rational' design of vaccines implies an understanding of the immune system at a similar level of discernment. It is also likely that many more new vaccines will have benefitted humanity well before such understandings will have become available. Notwithstanding the evident scientific excellence of the work of Almond and his collaborators, the progress towards a safer type III live polio vaccine has been steady and seems sure to emerge with the required product. By contrast the work which Mackett described would seem to confine the recombinant vaccinia based vaccines to the maws of the regulatory agencies for the forseeable future. Just how does one go about generating evidence that a 'scientifically' attenuated virus will cause fewer than one hospitalisation in 30 000 vaccinees when the number of people one is allowed to vaccinate fall well short of that large figure ? The prospect of offering vaccines to the developing world would not provide the data to satisfy the regulatory agencies of the safety of such vaccines as (a) it is not possible to monitor vaccinees to discover possible abreactions and (b) the problems of vaccination in a situation where many other diseases are prevalent may mask any abreactions due to the vaccine or may attribute unwarranted diseases to the vaccine. While such niceties are debated, people are denied an opportunity to hazard themselves in a situation where the risks are small relative to the magnitude of the gains.
On the bacterial side the main loci of activity were (a) the enterotoxic diseases caused by Salmonella, Shigella, enterotoxigenic Escherichia and Cholera, (b) the lung diseases caused by Pseudomonas, Haemophilus and Bordetella and (c) an assortment of human diseases as widely separated as gonorrhoea, dental caries and tetanus. Veterinary vaccines were represented by a single paper on blackwater disease in Nigeria. Considerable progress has been made in the establishment of a bacterial carrier for immunogens. This work, based on the use of the Ty21a strain of Salmonella takes advantage of the requirement of this organism for galactose. This limitation enables the organism to be grown in culture yet when it is admitted into the gut of the vaccinee the local concentration of the limiting nutrient is such that the organism cannot flourish. It is thus inactivated at the site of action which obviates all those methods of inactivation which have been shown to necessarily and concommitantly decrease the immunogenic activity of putative vaccines (Germanier). The development of such an organism as a vector for other bacterial antigens is under active investigation. The analysis of the detailed structure of the outer membrane proteins of Shigella dysenteria (Timmis) and of the polysaccharides at the surface of Pseudomonas aeruginosa (Cryz) has enabled investigators to design, construct and test a range of new formulation as vaccines. Such materials offer promise of prophylaxis for the diseases caused by these organisms. In a more contentious sense the immunogens of Streptococcus mutans, protective against dental caries, have been shown to be active in protecting simians against infection yet there seems to be little activity in translating these observations into a vaccine for humans (Russel). On the other hand work on a subunit pertussis vaccine (Robinson) which is safer and more immunogenic than earlier preparations is in hand. It also differs from the equivalent Japanese vaccine in that it can be prepared to a more consistent standard. There are clearly many new developments in the pipeline. When they will see the light of day depends not only on the technical properties of the materials but also on those who have the responsibility for determining the balance of the risks and the gains.
R.E. Spier
Vaccine, Vol. 4, December 1986
277
By way of contrast, the papers presented in the virus vaccine session lacked the edge that was evident in the bacterial presentations. It is clear that the simpler structure of viruses has led to complete three-dimensional descriptions at the atomic level for the small icosohedral particles of poliovirus and rhinovirus. Such knowledge is at present being exploited by those who wish to develop new subunit vaccines for the diseases mentioned and also for foot-and-mouth disease. The hypothesis that such a detailed knowledge of the structure of the virus would lead to a new generation of 'scientific vaccines' is clearly under test at this time. It could be that knowledge of the structure of the infectious particle is insufficient and that the 'rational' design of vaccines implies an understanding of the immune system at a similar level of discernment. It is also likely that many more new vaccines will have benefitted humanity well before such understandings will have become available. Notwithstanding the evident scientific excellence of the work of Almond and his collaborators, the progress towards a safer type III live polio vaccine has been steady and seems sure to emerge with the required product. By contrast the work which Mackett described would seem to confine the recombinant vaccinia based vaccines to the maws of the regulatory agencies for the forseeable future. Just how does one go about generating evidence that a 'scientifically' attenuated virus will cause fewer than one hospitalisation in 30 000 vaccinees when the number of people one is allowed to vaccinate fall well short of that large figure ? The prospect of offering vaccines to the developing world would not provide the data to satisfy the regulatory agencies of the safety of such vaccines as (a) it is not possible to monitor vaccinees to discover possible abreactions and (b) the problems of vaccination in a situation where many other diseases are prevalent may mask any abreactions due to the vaccine or may attribute unwarranted diseases to the vaccine. While such niceties are debated, people are denied an opportunity to hazard themselves in a situation where the risks are small relative to the magnitude of the gains.
On the bacterial side the main loci of activity were (a) the enterotoxic diseases caused by Salmonella, Shigella, enterotoxigenic Escherichia and Cholera, (b) the lung diseases caused by Pseudomonas, Haemophilus and Bordetella and (c) an assortment of human diseases as widely separated as gonorrhoea, dental caries and tetanus. Veterinary vaccines were represented by a single paper on blackwater disease in Nigeria. Considerable progress has been made in the establishment of a bacterial carrier for immunogens. This work, based on the use of the Ty21a strain of Salmonella takes advantage of the requirement of this organism for galactose. This limitation enables the organism to be grown in culture yet when it is admitted into the gut of the vaccinee the local concentration of the limiting nutrient is such that the organism cannot flourish. It is thus inactivated at the site of action which obviates all those methods of inactivation which have been shown to necessarily and concommitantly decrease the immunogenic activity of putative vaccines (Germanier). The development of such an organism as a vector for other bacterial antigens is under active investigation. The analysis of the detailed structure of the outer membrane proteins of Shigella dysenteria (Timmis) and of the polysaccharides at the surface of Pseudomonas aeruginosa (Cryz) has enabled investigators to design, construct and test a range of new formulation as vaccines. Such materials offer promise of prophylaxis for the diseases caused by these organisms. In a more contentious sense the immunogens of Streptococcus mutans, protective against dental caries, have been shown to be active in protecting simians against infection yet there seems to be little activity in translating these observations into a vaccine for humans (Russel). On the other hand work on a subunit pertussis vaccine (Robinson) which is safer and more immunogenic than earlier preparations is in hand. It also differs from the equivalent Japanese vaccine in that it can be prepared to a more consistent standard. There are clearly many new developments in the pipeline. When they will see the light of day depends not only on the technical properties of the materials but also on those who have the responsibility for determining the balance of the risks and the gains.
R.E. Spier
Vaccine, Vol. 4, December 1986
277