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‘Concealed’ antigens: expanding the range of immunological targets
334 that strategies for developing vaccines against malada must be dependent upon identifying the roles that a vadety of cytokines play in the development and expression of immunity to various stages of Plasmodium parasites. To this end, studies are in progress in our laboratory to investigate the roles ofTHI and TH2 derived cytokines in protection versus exacerbation during non-lethal and lethal blood-stage P. chabaudi AS infection. We are addressing these questions in vivo and in vitro. The need to address similar questions in humans is obvious, albeit more difficult to pursue than in an animal model such as
Antimalarial Resistance and Health Policies In Africa, gathering information on resistance of Plasmodium falciparum to antimalarial drugs is particularly expensive and difficult because of problems of follow-up and reinfection owing to the lack of resources and local personnel available to perform the specialized tests which are required. Indeed, introduction of such investigations could divert meagre resources from projects which are perceived as having a higher priority, such as AIDS, infant nutrition or vaccination campaigns. At the present time, most of our knowledge of the susceptibility of P. fdlciparum in Africa has been obtained either from anecdotal reports or special surveys. Unfortunately, the results of such studies usually become available months and perhaps years after completion of the study when it is possible that patterns of sensitivity
'Concealed' Antigens: Expanding the Range of Immunological Targets Peter Willadsen and colleagues I have demonstrated an important and successful approach to the development of antiparasite vaccines. However, there are two points worth noting concerning their discussion. (I) A whole group of'concealed' antigens have been described from Plasmodium: the so called transmission blocking antigens. Like Bm86, these membrane associated molecules were identified originally by crude immunization using the insect stages of Plasmodium ~, stages not normally seen by the vertebrate immune system. The similarities extend still further in that, while field trials of the P. falciparum sexual stage vaccine are forseeable3, the function of the native antigen is still unknown. (2) It is not impossible nor premature to develop a 'rational approach to vaccine
Parasitology Today, vol 9. no. 9, 1993 P. chabaudi. We hope that our approach
using a mouse model will provide a conceptual framework for establishing the immunobiology of cytokines in blood-stage malaria in humans. References
I Taveme, J. (1993) Parasitology Today 9, 38 39 2 Stevenson, M.M. and Tam, M-F. (1993) Clin Exp. Immunol. 92, 77 83 3 Langhome, J. et al. (f989) Int. Immunol. I. 416424 4 Meding, S. j. et al. ( 1991) Eu: j Immunol. 2 I, 1433 4438 5 Kumaratilake, L.M. and Ferrante, A. (1992) J. Immunol. 149, 194 199
have changed. Moreover, they measure onty response to infection and not malaria disease, and can only be performed on small samples of patients who meet eligibility criteria. Clearly, in order to provide more current information, continuous monitoring by local health personnel is urgently required. Data collected on the basis of systematized continuous reporting of treatment failure in a particular area by local health workers, could provide an indication of the lack of efficacy of a certain drug in that area. This approach is now part of the Global Strategy for malaria*. The cost of implementing such a routine early-warning system would be low, since additional facilities and personnel would not be required and training would be minimal. Existing health workers would be required to enter a minimum amount of
* See Report of the Ministerial Conference on Malaria,Amsterdam, 26 27 October 1992
design'. While I and my colleagues are immunizing with crude (concealed) antigens of mosquitoes at the moment 4, we have also had some success in identifying specific target sites in the mosquito midgut that are of interest, primarily for interrupting parasite transmission s. In particular, by examining in detail the insect stages of the parasite life cycle 6, we have taken the sequential steps (P.F. Billingsley, H. Hui and A. Sumner, abstract)*: of ( I ) identifying the possible role for carbohydrates on the midgut cell surface; (2) demonstrating binding of ookinetes to glycosylated substrates; and (3) blocking parasite transmission with selected sugar incorporated into the infective bloodmeal. Our next rational steps will be to identify the ligands on parasite and vector-midgut surfaces involved in this interaction, and subsequently immunize with these identified antigens to develop further candidate vaccines. Much is made of the limited knowledge concerning molecular biochemistry of * British Society of Parasitology4th Malaria Meeting, London, UK, 1992
6 Liew, F.Y. et al. (1991) Eur j. Irnmunol. 21, 2489 2494 7 Oswald, I.P. et al. (1992) j Immunol 148, 3578 3582 8 Gazzinelli, R.R. et al. (I 992) J. Immunol. 148, t792 1796 9 Silva, J.S. et al (1992) J. Exp. Med. 175, 169 t74 10 Kumaratilake, LM. and Ferrante, A. (1993) Parasitology Today 9, 56 57 Mary M. Stevenson
Montreal General HospitaJResearchInstitute and Department of Medicine McGill University Montreal, Quebec, Canada
data on cards which could be forwarded to district centres for data handling. In this way, notification of individual cases could be co-ordinated thus pin-pointing areas where sensitivity testing would be appropriate. Such a system should incorporate a systematic notification of treatment failures which may be defined on clinical grounds in the absence of laboratory facilities, as well as the determination of the proportion of treatment failures in a given population by simplified in vivo testing based on a minimum number of follow-up checks. Piero L. Olliaro
UNDP/VVorld Bank/VVorldHealth Organization SpecialProgrammefor Research and Training in Tropical Diseases CH- 121 I Geneva 27, Switzerland Peter I. Trigg
MalariaUnit, Division of Control of Tropical Diseases World Health Organization CH 121 t Geneva 27, Switzerland
vectors, parasites and their interactions. However, there is much that we do know and much that can be inferred from other systems4; in many cases, what we do know has never been put to the 'acid test' of development for vector and parasite vaccines. This is still possible within the concept of presenting concealed parasite or vector antigens for vaccination purposes. References
I Wil[adsen, P., Eisemann,C.H. and Tellam, R.L (I 993) Parasitology Today 9, 132 135 2 Carter, R. et al. (1988) Prog. Allergy 4t, 193 214 3 Kaslow, D.C., Bathurst, I.C. and Barr, P.J. (1992) Trends Biotechnol. I0, 388 391 4 Billingsley,P.F. Trans. R. Soc. Trop. Med. Hyg. (in press) 5 Billingsley,P.F.Int.j Parasitol (in press) 6 Miller, L.H and Warburg, A. (1991) Parasitology Today 7, 179 18 I Peter F. Billingsley
Department of Biology Imperial College of Science,Technology and Medicine Prince Consort Road London, UK SW7 2BB
Antimalarial Resistance and Health Policies In Africa, gathering information on resistance of Plasmodium falciparum to antimalarial drugs is particularly expensive and difficult because of problems of follow-up and reinfection owing to the lack of resources and local personnel available to perform the specialized tests which are required. Indeed, introduction of such investigations could divert meagre resources from projects which are perceived as having a higher priority, such as AIDS, infant nutrition or vaccination campaigns. At the present time, most of our knowledge of the susceptibility of P. fdlciparum in Africa has been obtained either from anecdotal reports or special surveys. Unfortunately, the results of such studies usually become available months and perhaps years after completion of the study when it is possible that patterns of sensitivity
'Concealed' Antigens: Expanding the Range of Immunological Targets Peter Willadsen and colleagues I have demonstrated an important and successful approach to the development of antiparasite vaccines. However, there are two points worth noting concerning their discussion. (I) A whole group of'concealed' antigens have been described from Plasmodium: the so called transmission blocking antigens. Like Bm86, these membrane associated molecules were identified originally by crude immunization using the insect stages of Plasmodium ~, stages not normally seen by the vertebrate immune system. The similarities extend still further in that, while field trials of the P. falciparum sexual stage vaccine are forseeable3, the function of the native antigen is still unknown. (2) It is not impossible nor premature to develop a 'rational approach to vaccine
Parasitology Today, vol 9. no. 9, 1993 P. chabaudi. We hope that our approach
using a mouse model will provide a conceptual framework for establishing the immunobiology of cytokines in blood-stage malaria in humans. References
I Taveme, J. (1993) Parasitology Today 9, 38 39 2 Stevenson, M.M. and Tam, M-F. (1993) Clin Exp. Immunol. 92, 77 83 3 Langhome, J. et al. (f989) Int. Immunol. I. 416424 4 Meding, S. j. et al. ( 1991) Eu: j Immunol. 2 I, 1433 4438 5 Kumaratilake, L.M. and Ferrante, A. (1992) J. Immunol. 149, 194 199
have changed. Moreover, they measure onty response to infection and not malaria disease, and can only be performed on small samples of patients who meet eligibility criteria. Clearly, in order to provide more current information, continuous monitoring by local health personnel is urgently required. Data collected on the basis of systematized continuous reporting of treatment failure in a particular area by local health workers, could provide an indication of the lack of efficacy of a certain drug in that area. This approach is now part of the Global Strategy for malaria*. The cost of implementing such a routine early-warning system would be low, since additional facilities and personnel would not be required and training would be minimal. Existing health workers would be required to enter a minimum amount of
* See Report of the Ministerial Conference on Malaria,Amsterdam, 26 27 October 1992
design'. While I and my colleagues are immunizing with crude (concealed) antigens of mosquitoes at the moment 4, we have also had some success in identifying specific target sites in the mosquito midgut that are of interest, primarily for interrupting parasite transmission s. In particular, by examining in detail the insect stages of the parasite life cycle 6, we have taken the sequential steps (P.F. Billingsley, H. Hui and A. Sumner, abstract)*: of ( I ) identifying the possible role for carbohydrates on the midgut cell surface; (2) demonstrating binding of ookinetes to glycosylated substrates; and (3) blocking parasite transmission with selected sugar incorporated into the infective bloodmeal. Our next rational steps will be to identify the ligands on parasite and vector-midgut surfaces involved in this interaction, and subsequently immunize with these identified antigens to develop further candidate vaccines. Much is made of the limited knowledge concerning molecular biochemistry of * British Society of Parasitology4th Malaria Meeting, London, UK, 1992
6 Liew, F.Y. et al. (1991) Eur j. Irnmunol. 21, 2489 2494 7 Oswald, I.P. et al. (1992) j Immunol 148, 3578 3582 8 Gazzinelli, R.R. et al. (I 992) J. Immunol. 148, t792 1796 9 Silva, J.S. et al (1992) J. Exp. Med. 175, 169 t74 10 Kumaratilake, LM. and Ferrante, A. (1993) Parasitology Today 9, 56 57 Mary M. Stevenson
Montreal General HospitaJResearchInstitute and Department of Medicine McGill University Montreal, Quebec, Canada
data on cards which could be forwarded to district centres for data handling. In this way, notification of individual cases could be co-ordinated thus pin-pointing areas where sensitivity testing would be appropriate. Such a system should incorporate a systematic notification of treatment failures which may be defined on clinical grounds in the absence of laboratory facilities, as well as the determination of the proportion of treatment failures in a given population by simplified in vivo testing based on a minimum number of follow-up checks. Piero L. Olliaro
UNDP/VVorld Bank/VVorldHealth Organization SpecialProgrammefor Research and Training in Tropical Diseases CH- 121 I Geneva 27, Switzerland Peter I. Trigg
MalariaUnit, Division of Control of Tropical Diseases World Health Organization CH 121 t Geneva 27, Switzerland
vectors, parasites and their interactions. However, there is much that we do know and much that can be inferred from other systems4; in many cases, what we do know has never been put to the 'acid test' of development for vector and parasite vaccines. This is still possible within the concept of presenting concealed parasite or vector antigens for vaccination purposes. References
I Wil[adsen, P., Eisemann,C.H. and Tellam, R.L (I 993) Parasitology Today 9, 132 135 2 Carter, R. et al. (1988) Prog. Allergy 4t, 193 214 3 Kaslow, D.C., Bathurst, I.C. and Barr, P.J. (1992) Trends Biotechnol. I0, 388 391 4 Billingsley,P.F. Trans. R. Soc. Trop. Med. Hyg. (in press) 5 Billingsley,P.F.Int.j Parasitol (in press) 6 Miller, L.H and Warburg, A. (1991) Parasitology Today 7, 179 18 I Peter F. Billingsley
Department of Biology Imperial College of Science,Technology and Medicine Prince Consort Road London, UK SW7 2BB