Pergamon

PARASITE IMMUNOLOGY SYMPOSIUM Chairperson: Antonio Ferrante

Women’s and Children’s Hospital, Adelaide, SA, Australiu

Over the last 20 years there has been a marked decline in our abilities to treat malaria because of resistance to many of the antimalarial drugs, and this problem has been exacerbated by insecticide resistance which has significantly affected efforts to control trans- mission of the parasite. These events have greatly com- pounded the global malaria problem caused by Plasmodium, with an estimated 2 million deaths and 200-300 million new infections per year of malaria. Activities to produce a malaria vaccine have con- tinued to intensify, mainly in the direction of an anti- parasite vaccine, but in addition an anti-disease vaccine is also under consideration. Treating the path- ology of malaria with anti-cytokine agents has also attracted interest, as it has in other diseases.

These activities attempting to address the malaria problem were evident in the 3 presentations delivered at the Symposium. The dedication towards the devel- opment of a subunit vaccine which targets the sexual and sporogonic stages was expressed by David Kaslow, National Institutes of Health. This formed the basis of a transmission-blocking vaccine candidate which has been developed and expressed in a recom- binant DNA expression system. Two candidate vac- cines described with transmissional blocking activity in laboratory animals were recombinant Pfs25 and Pfs28, the Pfs25 being tested at present in human Phase 1 clinical trials. Other potential vaccine can- didates were also described. As with the vaccines directed against the sporozoite, liver stage and asexual blood stage, transmission-blocking vaccine has its unique place in strategies to combat malaria by reduc- ing its transmission. A detailed account was presented of the use of transmission-blocking vaccines to achieve the long-term goal of malaria eradication by an easily administered and inexpensive product.

It is evident that a lack of appropriate under- standing of the mechanisms of host resistance to infec- tion and protection against pathology in malaria has been responsible for the slow progress in the devel- opment of a malaria vaccine. Understanding the role of ;sii T cells in malaria infections may provide insights

into natural immune processes in this disease, which may then contribute to the development of better vac- cine strategies. Christine Rzepczyk, Queensland Insti- tute of Medical Research, emphasised that 116 7‘ cells are important in the host response to maiarial infec- tions. A description of the ways in which y6 T cells may contribute to host protection or host pathology in malaria was presented. This included a description of the ability of 76 T cells to inhibit replication of asexual blood stages of Plasmodium, either directly

or indirectly, by activating other cell populations via secreted cytokines. p6 T cells were also perceived to play a role in the regulation of the immune response. Since $J T cells produce cytokines of the Thl type, with a predominance of IFN-y and TNF, the acti- vation of large subpopulations of these cells by malaria antigens was suggested as a possible pre- disposing factor to host pathophysiology.

Treating the illness in malaria has been a goal since the original description that protection and pathology in malaria were “two sides of the same coin”. Efforts have therefore been made to inhibit cytokines sus- pected to be responsible for the pathology. Anti-TNF therapy has been one approach. In this symposium, Deborah Rathjen from the Adelaide Women’s and Children’s Hospital described some of the new devel- opments on this front. She described molecules which were engineered to inhibit the pathogenetic effects of TNF. Short peptides of 10-l 5 amino acid residues representing sequences of the TNF molecules have been made and were shown to inhibit TNF activity in vitro and in mice as assessed by their ability to prevent TNF-induced hypoglycaemia in mice infected with Plasmodium herghei. These molecules are of interest because of their ability to diffuse easily into tissue sites, and may be administered via nasal spray.

This Symposium, while highlighting the difficulties involved in understanding the immune responses to malaria and the complexities in malaria vaccine devel- opment, has also given cause for optimism that the research now being undertaken can lead to improved malaria control and disease management.

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