Immunology and world health: key contributions from the global community.

The contributions of immunology to world health must be seen in the context of the severe disadvantage prevailing in many countries. Low life expectancy, high infant and maternal mortality rates, and continued prevalence of infections as causes of preventable deaths highlight what vaccines can do to improve the situation. This paper will briefly review some major new international health programs, including the GAVI Alliance; the Global Polio Eradication Initiative; the Global Fund to Fight AIDS, Tuberculosis and Malaria; the President's Emergency Plan for AIDS Relief; and the Global Malaria Action Plan. It will also outline the state of research progress for vaccines that are not yet licensed but that, in many cases, appear within reach. Of course, vaccines are not the be-all and the end-all of global health, so brief reference will be made to nutrition, vector biology and control, and the emergence of noncommunicable diseases as threats.

Vaccines of the future.

Vaccines of the future can be divided into three broad groups, namely those of the near future (<10 years); the medium-term future (10-19 years); and the long-term future (20-50 years). For the near future, there is some "low hanging fruit" which is clearly on the horizon, such as a Vi-conjugate vaccine for typhoid or a protein-based vaccine for Neisseria meningitidis serogroup B. Just slightly more distant will be vaccines for shigellosis and a common protein vaccine for Streptococcus pneumoniae. Also in this group, but not as far advanced, will be a vaccine for Group A streptococcus. I place vaccines for the "big three", malaria, tuberculosis and HIV/AIDS in the medium term basket. The sporozoite malaria vaccine RTS-S is closest, but surely a definitive malaria vaccine will also require antigens from other stages of the life cycle. A tuberculosis vaccine will be either a re-engineered BCG; or a molecular vaccine with several protein antigens; or one based on prime-boost strategies. What will delay this is the high cost of clinical trials. For HIV/AIDS, the partial success of the Sanofi-Pasteur prime-boost vaccine has given some hope. I still place much faith in antibody-based vaccines and especially on mimotopes of the env transitional state assumed after initial CD4 binding. Monoclonal antibodies are also leading us in interesting directions. Longer term, the vaccine approach will be successful for autoimmune diseases, e.g. juvenile diabetes and coeliac disease. Cancer vaccines are also briefly surveyed. Adjunct issues needing to be addressed include more extensive combinations; alternate delivery systems; and more intelligently designed adjuvants based on knowledge of the innate immune system.

Vaccines and future global health needs.

Increased international support for both research into new vaccines and their deployment in developing countries has been evident over the past decade. In particular, the GAVI Alliance has had a major impact in increasing uptake of the six common infant vaccines as well as those against hepatitis B and yellow fever. It further aims to introduce pneumococcal and rotavirus vaccines in the near future and several others, including those against human papillomavirus, meningococcal disease, rubella and typhoid not long after that. In addition, there is advanced research into vaccines against malaria, HIV/AIDS and tuberculosis. By 2030, we may have about 20 vaccines that need to be used in the developing world. Finding the requisite funds to achieve this will pose a major problem. A second and urgent question is how to complete the job of global polio eradication. The new strategic plan calls for completion by 2013, but both pre-eradication and post-eradication challenges remain. Vaccines will eventually become available beyond the field of infectious diseases. Much interesting work is being done in both autoimmunity and cancer. Cutting across disease groupings, there are issues in methods of delivery and new adjuvant formulations.

A healthier climate for the funding of vaccine research.

Vaccination is a marvel of scientific endeavor that benefits the masses. Yet the laissez-faire economy may not provide a sufficient push for vaccine research and development. The current climate that drives this globally important venture is examined here.

One cell, one antibody: prelude and aftermath.

This essay seeks to summarize one scientist's pilgrim's progress through the world of antibody formation, attempting to capture the flavor of problems as encountered within their times. It seeks to portray a world where the direct template hypothesis ruled the day, where the function of lymphocytes was unknown, let alone the difference between T and B cells, and where antibody genes were but a dream. Struggles to establish the credentials of the clonal selection hypothesis are presented in some detail, as are the implications which followed the 'one cell - one antibody' discovery. The other two main preoccupations of the author are presented more briefly, namely the essential features of the germinal center and the cellular basis of immunological tolerance within the B lymphocyte compartment. Naturally, the experiments become more sophisticated as both knowledge and technology mature. A continuing thread within the unfolding story is that one must not shy away from developing new techniques when problems demand them.

Funding options for research: facing the market as well as government.

Parasitology is a challenge. At one level, the structural and genetic complexities of parasites provide ample technical challenges in regard to an understanding of parasite variability and adaptability, epidemiological diversity, drug resistance, etc. The intricacies of host parasite relationships including the immunology of parasitism will continually surprise yet frustrate the vaccine developer and keep the bravest immunoparasitologist busy and creative for decades. As if the technical considerations were not challenging enough, we see difficulties arising in sustaining a research endeavour and preserving a critical mass of researchers through the generation of high-level, long-term funding support. Contributing to this situation is the fact that most parasitic diseases of major impact in humans are largely centred around the rural poor in tropical, less industrially-developed countries and therefore of little or of fickle interest to the strictly commercially oriented. Moreover, the focus in the rural industries has moved away from aspects of on-farm production with lower priority given to studies on even the 'economically-important' parasites of livestock. It is contended that this may change again with pressures and clear marketing advantages to preserving a 'clean and green' image for Australia's primary industries. Overall, the extraordinary technical and conceptual advances in recent times have been tempered by uncertainties in research funding and severe cuts from some traditional sources for both fundamental and strategic/applied research in Parasitology. Several have highlighted the fact that deliverables in terms of new methods of disease control have been sparse and some claims made in the past have certainly been exaggerated. Yet the prospects and achievements at the front end of the long R&D pathway have never been brighter. In this article we examine the merits of a 'portfolio approach' to generating research funds in Parasitology and Science and Technology in Australia more generally, with an emphasis on strategies that, through welding good science with clear, medium-term product objectives, increase research funding opportunities.