Humoral Immune Responses in Volunteers Immunized with Irradiated Plasmodium falciparum Sporozoites

Protective Immunity Induced with Malaria Vaccine, RTS,S, Is Linked to Plasmodium falciparum Circumsporozoite Protein-Specific CD4+ and CD8+ T Cells Producing IFN-γ

“…Furthermore, by enhancing the Ab response (14), an important protective mechanism against the spz stage infection, IFN-␥ might be a key cytokine that integrates the multifactorial protective immune responses to exo-erythrocytic parasites. RTS,S vaccination induces a substantial CS protein repeat region-specific Ab response (2-4), which generally exceeds the anti-repeat Ab levels described in subjects protected by attenuated P. falciparum spz (6). A statistical analysis by Spearman's rank test demonstrated a positive correlation between the RTS,S-induced IFN-␥ responses shown here and CS protein repeat-specific Ab titers (micrograms per milliliter) reported previously for the same group of subjects (2), with a coefficient of 0.573 and p Ͻ 0.008.…”

“…There is ample evidence from studies of immune responses elicited by natural exposure to Plasmodia parasites and experimental immunization with attenuated Plasmodia spz to support a protective role of B cells (5,6) and CD4 ϩ (7-9) and CD8 ϩ (10 -13) T cells specific for exo-erythrocytic Ags. Although both T cell subsets exhibit many functional properties, CD4 ϩ T cells principally help, whereas CD8 ϩ T cells directly exert protective effector function by several distinct mechanisms.…”

Induction of Plasmodium falciparum sporozoite-neutralizing antibodies upon vaccination with recombinant Pfs16 vaccinia virus and/or recombinant Pfs16 protein produced in yeast

“…After rupture of hepatocytes, these merozoites initiate repeated cycles of erythrocyte infection associated with clinical disease. Irradiated sporozoites elicit protective immunity in rodents, monkeys and humans and led to the identifi cation of the circumsporozoite (CS) protein and the sporozoite surface 2 protein (SSP2) [1][2][3][4][5]. There is now compelling evidence indicating that the immu nity induced by irradiated sporozoites is mediated by anti-sporozoite antibodies, as well as CD4 4-and CD8 + cells that recognize sporozoite-infected hepa tocytes [6 ].…”

Pre–erythrocytic–stage immune effector mechanisms inPlasmodiumspp. infections

“…Sterile protective immunity against Plasmodium berghei, P. knowlesi, P. falciparum or P. vivax sporozoite challenge has been induced by immunization with radiation-attenuated sporozoites in every model system tested, including mice (Nussenzweig et al 1969), monkeys (Gwadz et al 1979) and humans (Clyde et al 1973a(Clyde et al ,b, 1975Rieckmann et al 1974Rieckmann et al , 1979Herrington et al 1991;Edelman et al 1993;Egan et al 1993). With reference to the blood stage, in chickens and turkeys, humoral-mediated transmission blocking immunity has developed after immunization with killed asexual-stage parasites (Hu¡ et al 1958); in monkeys, persistent blood-stage infection has been cleared by immunization with P. knowlesi asexual-stage parasites in adjuvant (Mitchell et al 1975); and in monkeys (Diggs et al 1972) and humans (Cohen et al 1961;McGregor & Carrington 1963;Bouharoun Tayoun et al 1990;Sabchareon et al 1991), passive transfer of puri¢ed immunoglobulin from individuals with lifelong malaria exposure to naive recipients has resulted in a marked decrease in P. falciparum bloodstage parasitaemia.…”