leidoscope Malaria vaccine strategy Michael Good's impression (Immunol. Today 1992, 13,126-129) that current malaria "blood stage vaccine design strategy is centered entirely on humoral immunity" makes it clear that those involved in malaria vaccine development need to be more explicit in describing the operative strategies currently in use. The important (but not exclusive) role of the spleen and of non-antibody-dependent mechanisms is widely appreciated. His belief that the "easiest way to induce suitable splenic modification ... [as an element in the development of immunity is] ... by malaria infection" is shared by others. Malaria mortality occurs almost exclusively during early childhood. Thereafter, effective naturally acquired immunity against disease, but not infection, becomes operative, and is maintained through continued infection. Currently, there is considerable emphasis on first generation vaccines which will decrease this mortality, while not preventing infection, and in the process allow naturally occurring immunity to develop. This result would be similar to that produced by an attenuated vaccine. Good believes that the blood-stage i~

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The legacy of von Behring and Kitasato As one who has published a review 1 on the 1890 classic paper of von Behring and Kitasato, I read with interest the Kaleidoscope article by F.J. Grundbacher (Immunol. Today 1992, 13, 188-190) on von Behring's discovery of diphtheria and tetanus antitoxins. May I make some related observations on yon Behring's legacy to immunology? First, in my review 1, I commented on the possible reasons for the exclusion of Kitasato in preference to yon Behring for the very first Nobel prize in medicine. Von Behring was not even in the original list of 46 nominees or the shortlist of 15 nominees for the 1901 prize, while Kitasato featured in both these lists. The medical historian Dolman noted that "The foibles of human judgement are sometimes reflected even in the decisions of the august Nobel Committee. A far less figure,

malaria vaccine effort is focused on antibody-mediated effector mechanisms only and seems to equate the use of subunit vaccines with attempts to induce antibodies only. Whereas the delivery of antigens in living carrier systems has been shown to favor the induction of cellular immune effector functions, CD4 + T-cell activation is also initiated by extracellular antigen. Naturally acquired immunity to blood-stage malaria is likely to involve macrophage phagocytosis, antigen processing, and antigen presentation. Similar pathways could proceed after immunization with subunit vaccines, especially through the use of appropriate adjuvants, although there is still little consensus on how to control specific immune responses, especially with respect to the induction of type 1 versus type 2 CD4 + T cells. The attentuated vaccine approach suggested was validated in principle many years ago through the induction of resistance to malaria using irradiated parasitized erythrocytes ~, and there are several quite recent papers on the subject (Ref. 2 and papers cited therein). However, a realistic strategy based on this principle is not yet feasible. As indicated by Good, and elaborated by Eleanor Riley i

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The US Agency for International Development, Malaria Vaccine Development Program, Atlantic Resources Corporation, Washington, DC, USA. References 1 Sadun, E.H., Wellde, B.T. and Hickman, R.L. (1969) Mil. Med. 134, 1165-1175 2 Mons, B. (1991) Acta Leidensia 60, 181-190

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von Behring, whose shabby treatment of Ehrlich the latter forgave, received the coveted award 7 years earlier, in 1901, for his work on serum therapy ... which could never have been accomplished without Ehrlich's help ''2. Secondly, though yon Behring's classic paper of 1890 on tetanus antitoxin was coauthored with Kitasato, yon Behring did not mention his Japanese collaborator's name even once in his entire Nobel lecture 3. As noted by Lindenmann 4, von Behring also did not use the word 'anti-toxin' in his single author paper s, published a week after the joint paper with Kitasato. Thirdly, the attribution quoted from the New Encyclopedia Britannica that yon Behring is "the founder of the science of immunology" is somewhat simplistic and misleading. To be precise, yon Behring may be identified as one of the pioneers who sowed their intellectual seeds for the origin of immunology as a discipline. However, the significant contributions of yon

Immunology Today

(Immunol. Today 1992, 13, 129130), the approaches he suggests could lead to usable vaccines only after several major technological advances are realized. A major challenge now is to balance efforts that may produce practical results soon with more imaginative ideas that might pay off later. Good's statement that "the strategy for inducing cellular immunity to malaria ... [should involve] ... less attention ... to specific target antigens and more to delivery strategies and nonspecific modification" could give the appearance of contradicting his later assertion that his "aim is not to devalue attempts at improving subunit vaccines". Readers should be as fully aware of the second assertion as they are of the first. Carter Diggs

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Behring's contemporaries such as Koch, Kitasato, Ehrlich, Bordet, Metchnikoff and Landsteiner were equally important to the development of immunology during the past century 6.

Sachi Sri Kantha

Osaka BioScience Institute, 6-2-4 Furuedai, Suita, Osaka 565, ]apan. References 1 Sri Kantha, S. (1991) KeioJ. Med. 40, 35-39 2 Dolman, C.E. (1962) Can.]. Public Health 53,269-278 3 yon Behring, E. (1989; Nobel Lecture of 12 Dec. 1901) Scand. J. Immunol. 30, 6-11 4 Lindenmann, J. (1984) Scand. J. Immunol. 19, 281-285 5 yon Behring, E. (1890) Dtsch. Med. Wochenschr. 16, 1145-1148 6 Miles A. (1990) in General Bacteriology and Immunity (Vol. 1) (8th edn) (Linton, A.H. and Dick, H.M., eds), pp. 2-14, Edward Arnold

Vol. 13 No. 9 1992

Malaria vaccine strategy.

leidoscope Malaria vaccine strategy Michael Good's impression (Immunol. Today 1992, 13,126-129) that current malaria "blood stage vaccine design strat...
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