T.W. Jones
Centre for Tropical Veterinary Medicine, University of Edinburgh, Easter Bush, ROSLIN, Midlothian, Scotland, UK, EH25 9RG
The past
The present
The future?
References
The ability of Salivarian trypanosomes to counter the host's immune system by producing a large number of antigenically different populations throughout the course of infection in the vertebrate host has fascinated scientists since early in the 20th century (Ritz, 1916) and continues to frustrate our efforts to produce an effective vaccine against trypanosomiasis (Turner, 1992).
The late 1960s and early 70's can be thought of as the "golden age" for serodeme analysis with much of the work carried out at research stations in Africa. Fundamental studies such as those of Gray who established many of the basic tenets of antigenic variation, notably, the idea that antigenic variation appeared to be an organised process with a tendency for certain antigen types to appear early in infection irrespective of the infecting variant (PREDOMINANT ANTIGEN TYPES) and the reversion to a particular antigen type after cyclical transmission (BASIC ANTIGEN). The ability to associate sequences of predominant antigens (REPERTOIRES) and basic antigens with particular isolates of trypanosomes provided a means of classifying trypanosome isolates into groups or SERODEMES. The work carried out during this period has been extensively reviewed by Gray, 1967; Lumsden, 1967; Gray and Luckins, 1976).
Refinement of many of the techniques originally developed in the 1960s, in particular the use of cloned populations and standardisation of terminology for variant antigen types (VATs) (Lumsden, 1982), led to an expansion of studies on serodeme analysis in laboratories outside Africa. Serodeme analysis offered a way of classifying a range of morphologically identical trypanosome isolates according to a functional characteristic as protective immunity is variant specific. The principal assumption behind these studies was that isolates with similar antigenic repertoires should show a higher degree of cross-immunity than those with dissimilar repertoires and hopefully lead to the development of immunoprophylactic methods of control. Because of the technical difficulties inherent in an immunological approach to serodeme analysis most studies on serodeme analysis concentrated on the easily handled T. brucei with the more technically demanding but economically more important species such as T. vivax receiving scant attention.
Results with T. brucei were disappointing, however, as large number of serodemes of T. brucei were identified even in a limited area. Studies with one of the trypanosome species causing human sleeping sickness - T. gambiense however, suggested that antigenic diversity between isolates of T. gambiense was much more limited than had been found in T. brucei. Isolates of T. gambiense from widely separated areas of Nigeria were found to produce a large number of variable antigens, in common (Gray, 1972). This was later expanded to include stocks from Nigeria, Senegal and Uganda and Zaire which also showed a high degree of similarity in their antigens based on the analysis of cloned populations (Gray, 1974). and in-vitro cultured metacyclic forms (Jones et al., 1981).
Since the 1980's there have been few studies carried out on antigenic relationships between trypanosome isolates. Most of these have been concerned with the non-tseste transmitted trypanosomes, especially T. evansi. An important concept in serodeme analysis in tsetse-transmitted trypanosomes was the use of metacyclic trypanosomes populations either as a source of infecting organisms or their analysis using monoclonal antibodies (Luckins et al., 1986). However, in the case of trypanosomes such as T. evansi metacyclic forms have never been described and the impact of this on antigenic development and diversity was unknown. Results from studies on T. evansi, however, showed antigenic variation proceeded in a similar way to that in tsetse-transmitted trypanosome species including the presence of predominant antigens (Jones and McKinnell, 1984; 1985a and 1985b), More importantly, however, antigenic diversity between stocks of T. evansi was far more limited than that reported in the tseste-transmitted trypanosomes (Jones and McKinnell, 1985c). This limited antigenic diversity probably stems from the non-cyclical nature of T. evansi transmission that limits the opportunity for genetic diversity. Limited antigenic diversity probably plays an important role in the epidemiology of T. evansi infection and is likely to be an important factor in the patterns of disease stability seen in areas such as Indonesia (Payne et al., 1991a; Payne et al., 1991b; Payne et al., 1992).
What does the future hold for serodeme analysis; how can we capitalise on the major advances made in molecular biology in the last decade?
Can we use molecular methods to simplify serodeme analysis without having to resort to extensive cloning and serological testing with batteries of antigenically different trypanosome populations?
Can we apply molecular methods to produce multi-variant vaccines for organisms such as T. gambiense and T. evansi that show limited antigenic diversity and what is the potential for multi-variant recombinant or DNA vaccines?
There is still (hopefully) a large amount of well characterised, cloned material available in several laboratories that could serve as a starting point for such studies but, in the current political and financial climate, support for the necessary international action is unlikely to be forthcoming.
Gray, A.R. and Luckins, A.G., 1976. Antigenic variation in Salivarian trypanosomes. In: The Biology of the Kinetoplastida. Ed W.H.R. Lumsden and D.A. Evans, Academic press, London, pp 493-542.
Gray, A.R., 1967. Some principles of the immunology of trypanosomiasis. Bulletin of the World Health Organisation, 37: 177-193.
Gray, A.R., 1974. Antigenic similarities among isolates of Trypanosoma gambiense from different countries in Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene, 68: 150-151.
Gray, A.R.. 1972. Variable agglutinogenic antigens of Trypanosoma gambiense and their distribution among isolates of the trypanosome collected in different places in Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 66: 263-284.
Jones T.W. and McKinnell, C.D., 1985b. Antigenic variation in Trypanosoma evansi: variable antigen type (VAT) composition of first relapse populations in mice. Tropical Medicine and Parasitology, 36: 127-130.
Jones T.W. and McKinnell, C.D., 1985c. Antigenic variation in Trypanosoma evansi: a comparison of the predominant variable antigen type repertoire of stocks from Sudan. Tropical Medicine and Parasitology, 36: 205-209.
Jones, T.W. and McKinnell, C.D., 1984. Antigenic variation in Trypanosoma evansi. Isolation and characterisation of variable antigen type populations from rabbits infected with a stock of T. evansi. Tropenmedizin und Parasitologie, 35: 237-241.
Jones, T.W. and McKinnell, C.D., 1985a. Antigenic variation in Trypanosoma evansi: variable antigen type development in mice, sheep and goats. Tropical Medicine and Parasitology, 36: 53-57.
Jones, T.W., Cunningham, I.C., Taylor, A.M., and Gray, A.R., 1981. The use of culture-derived metacyclic trypanosomes in studies on the serological relationships of stocks of Trypanosoma gambiense. Transactions of the Royal Society of Tropical Medicine and Hygiene, 75: 560-565.
Luckins, A.G., Frame, I.A., Gray, M.A., Crowe, J.S., and Ross, C.A., 1986. Analysis of trypanosome variable antigen types in cultures of metacyclic and mammalian forms of Trypanosoma congolense. Parasitology, 93: 99-109.
Lumsden, W.H.R., 1967. Trends in research on the immunology of trypanosomiasis. Bulletin of the World Health Organisation, 67: 167-175.
Lumsden, W.H.R., 1982. Characterisation and nomenclature of trypanosome serodemes and zymodemes: Report of a meeting held in Edinburgh September, 1978. Systematic Parasitology, 4:373-376.
Payne, R.C., Djauhari, D., Partoutomo, S., Wilson, A.J., Jones, T.W., Boid, R. and Luckins, A.G., 199 la. Trypanosoma evansi infection in cattle, buffaloes and horses in Indonesia. Veterinary Parasitology, 38: 109-119.
Payne, R.C., Sukanto, I.P. and Jones, T.W., 1992. Trypanosoma evansi as a constraint to livestock productivity in Indonesia. In: Proceedings of the First Seminar on N.T.T.A.T., Annecy, France, 14-16 October 1992: p 164.
Payne, R.C., Waltner-Toews, D., Djauhari, D. and Jones, T.W., 1991b. Trypanosoma evansi infection in swamp buffalo imported into Central Java. Preventive Veterinary Medicine, 11: 105-114.
Ritz, H., 1916. Über rezidive bei experimenteller trypansosomiasis II Miteilung. Archiv für Schiffsund Tropen-hygiene, 20: 397-420.
Turner, M.J., 1992. The biochemistry of the surface antigen of the African trypanosomes. British Medical Journal, 41: 137-43.
