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Chapter 46 : Immune Intervention in Malaria

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Abstract:

A parasite’s life cycle is complex, hence there are three major targets of vaccines. Overall, each of these stages is antigenically, morphologically, and biochemically distinct so that different researchers have focused on different stages, with different goals: sporozoites for prevention of infection or early liver stage development, erythrocytic stages to limit malaria morbidity and mortality, and the sexual stages to reduce transmission to others. This chapter reviews vaccine development efforts separated by stages of infection. A number of immunization studies using experimental animal models and humans performed in the 1960s and 1970s demonstrated that protective immunity against preerythrocytic stages of malaria parasites could be induced by immunization with irradiation-attenuated sporozoites. Since immunization of humans with radiation-attenuated sporozoites has been shown to induce consistently strong protective immunity and considering that this efficacy has not been matched by immunization with available subunit vaccines, some researchers have proposed the implementation of a large-scale vaccination program using attenuated sporozoites. The merozoite proteins can elicit immune responses that prevent red cell invasion and development while the red cell surface proteins can induce responses that promote elimination of infected red cells and limit binding to host cells. There has been an ongoing discussion as to whether a vaccine should be targeted to replicating the type of immunity found in a semi-immune adult or whether the goal of a vaccine should be to elicit responses superior to the partial immunity conferred by long-term and repeated exposure to malaria infection.

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46

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FIGURE 1

Life cycle of malaria parasites.

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46
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Image of FIGURE 2
FIGURE 2

Development of in human red blood cells. Merozoites attach to and invade mature red blood cells (RBCs) and the parasite develops in a parasitophorous vacuole through ring (0 to 24 hours), trophozoite (24 to 36 hours), and schizont stages (40 to 48 hours). In midcycle, membranous structures appear in the RBC cytoplasm and deformations (knobs) appear on the RBC membrane. These knobs include parasite-encoded proteins in the erythrocyte membrane protein-1 (PfEMP1) family as well as other proteins. After approximately 48 hours, the infected RBC ruptures and releases 16 to 32 daughter merozoites. Taken from Maier and colleagues ( ).

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46
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Image of FIGURE 3
FIGURE 3

Illustration of a malaria merozoite as well as major proteins located on the merozoite surface, the rhoptries, and the micronemes. Taken from Richards and Beeson ( ).

Citation: Long C, Zavala F. 2011. Immune Intervention in Malaria, p 587-597. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch46
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