Vaccination as a Control Measure
This chapter is introduced by a section describing the development of protective immunity and immunologic memory to Leishmania parasites and the most relevant immune mechanisms for designing vaccines. The following section deals with the first-generation
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Introduction: Immunity and Immunologic Memory to Leishmania Parasites During the last century, diverse vaccination strategies against leishmaniasis have been developed. The pioneer in vaccine development against leishmaniasis was Professor Saul Adler at the Hebrew University of Jerusalem, Israel. He recognized that mothers of Lebanon exposed their children’s arms to the bite of sand flies, since they intuitively knew that the development of a self-healing single first lesion would protect them from severe disease in future (Gavron and Saul 1997). Based on the early observation that the recovery from cutaneous leishmaniasis is followed by a strong immunity (Bray and Modabber 2000; Greenblatt 1980; Handman 1997; Senekji and Beattie 1941), the concept of leishmanization, one of the oldest forms of vaccination, was born. This type of active immunization with non-attenuated vaccines is based on the inoculation of virulent live parasites or tissue extracts from skin lesions into hidden areas of nonimmune individuals. This procedure was practiced since the 1970s in the Middle East (Israel, Iran, and republics of the former Soviet Union) to prevent lesions in visible areas of the human body (Handman 1997). While some individuals treated with virulent parasites developed long-term large lesions, which did not heal without treatment, others became chronic and did not respond to chemotherapy. Thus, this procedure completely failed as successful immunization strategy because of its high risk. Furthermore, leishmanization could not be used as feasible immunization method in humans, since standardization of leishmanization was not possible
K. F€arber • H. Moll (*) Institute for Molecular Infection Biology, University of W€urzburg, Josef-Schneider-St. 2/D15, W€urzburg 97080, Germany e-mail: [email protected] A. Ponte-Sucre et al. (eds.), Drug Resistance in Leishmania Parasites, DOI 10.1007/978-3-7091-1125-3_6, # Springer-Verlag Wien 2013
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due to the loss of virulence of cell-culture-derived parasites (Greenblatt 1980). Nevertheless, a prophylactic live vaccine, consisting of a mixture of live virulent Leishmania major mixed with killed parasites, is registered in Uzbekistan (Gafurov 1999; Sergiev 1992). The concept of using the protective properties of Leishmania without its danger potential was generated by Breton and colleagues. They utilized a nonpathogenic Leishmania species to immunize against virulent species (Roberts 2005). In this study, mice were immunized with the nonpathogenic species Leishmania tarentolae (Breton et al. 2005), with the aim to use the high level of immunological cross-reactivity between species. The results from this study with BALB/C mice appear promising (Breton et al. 2005), but vaccination with live non-attenuated parasites did not represent an appropriate option for human clinical studies. When scientists in the field investigated the immunological processes underlying immunity against leishmaniasis, they found in the mouse model that healing from
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