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Disease relevance of Sporozoites

  • Infections with Theileria parva and T. annulata can be prevented by the administration of carefully controlled numbers of sporozoites simultaneously with a long acting tetracycline and this form of immunization has been widely used for the control of East Coast fever in Africa with considerable success [1].
  • Over the last decade, bed nets impregnated with cheap and long-lasting pyrethroids used in Africa and Asia have shown their utility in reducing human-vector contact, inoculation of humans with sporozoites, clinical episodes of fever, and high levels of parasitemia [2].
  • Recombinant adenovirus, expressing the CS protein of Plasmodium yoelii, AdPyCS, was shown to induce a comparable degree of T cell-mediated protection against malaria as a single dose of irradiated P. yoelii sporozoites, causing inhibition of liver stage development [3].
  • Production in ascites fluid of biosynthetically labelled monoclonal antibody to Theileria parva sporozoites [4].
  • Plasmodium berghei sporozoites frozen in MEM (Eagle) medium supplemented with 10% hydroxyethyl starch and 50% normal mouse serum retained 0.5% infectivity to cultured hepatoma cells, compared to 6.8% before freezing [5].

Psychiatry related information on Sporozoites

  • In the search for subunit vaccines that are able to induce the type of sterile, protective immunity achieved by irradiated sporozoites, there is increasing evidence that defense mechanisms directed at the intrahepatic stage and Ags expressed at this stage are critical [6].

High impact information on Sporozoites

  • Cultured parasites were sensitive to primaquine, were shown to resemble parasites in living hosts by immunofluorescent antibody tests, and on subinoculation into mice induced a red blood cell infection, the gametocytes of which produced sporozoites in anopheline mosquitoes [7].
  • Liposomes containing neutral glycolipids with a terminal glucose or galactose, when injected intravenously, prevented the appearance of erythrocytic forms of malaria (Plasmodium berghei) in mice previously injected with sporozoites [8].
  • These findings suggest that malaria sporozoites utilize the interaction of the CS protein with HSPGs and LRP as the major mechanism for host cell invasion [9].
  • In addition, malaria sporozoites are less infective in LDL-receptor knockout (LDLR -/-) mice maintained on a high fat diet, as compared with littermates maintained on a normal diet [10].
  • Here we provide evidence that sporozoites, lactoferrin, and remnant lipoproteins are cleared from the blood by similar mechanisms [10].

Chemical compound and disease context of Sporozoites


Biological context of Sporozoites


Anatomical context of Sporozoites

  • Lectin-mediated and concentration-dependent binding of purified MBL was detected on sporozoites but not oocysts, and MBL activated C4 on sporozoites [19].
  • A substitution in a conserved residue of the A-domain or a deletion in the TSP motif of PfTRAP impairs the sporozoites' ability to invade mosquito salivary glands [20].
  • Although mice are not susceptible to infection by P. falciparum sporozoites, we demonstrated that administration of two distinct immunogens expressing PF3 elicited activated, extravasating CS-specific T cells that protected against an intracerebral VacPf challenge [21].
  • In this paper, in BALB/c mice, we establish that after immunization with irradiated sporozoites or DNA vaccines parasite-specific CD8+ T cells trigger a novel mechanism of adaptive immunity that is dependent on T cell- and non-T cell-derived cytokines, in particular IFN-gamma and IL-12, and requires NK cells but not CD4+ T cells [22].
  • Tick salivary gland extract and interleukin-2 stimulation enhance susceptibility of lymphocytes to infection by Theileria parva sporozoites [23].

Associations of Sporozoites with chemical compounds

  • P. berghei sporozoites bound specifically to sulfatide (galactosyl[3-sulfate]beta 1-1ceramide), but not to comparable levels of cholesterol-3-sulfate, or several examples of neutral glycosphingolipids, gangliosides, or phospholipids [24].
  • VacPf also greatly enhanced the primary response of mice injected with P. falciparum sporozoites or with a lipopeptide containing PF3 [21].
  • Immunization with sporozoites, which was conducted under chloroquine treatment to minimize the influence of blood stage parasites, induced a strong protection against a subsequent sporozoite and, to a lesser extent, against infected RBC challenges [25].
  • CSL was characterized as a soluble glycoprotein exoantigen released by infectious sporozoites [26].
  • We show in this report that antibodies to the N2 and C2 synthetic peptides react not only with P. knowlesi but also with conserved regions of the surface membrane of other human, monkey, and rodent (but not avian) malaria sporozoites [27].

Gene context of Sporozoites

  • Liver tissue from immunized mice expressed maximal levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with sporozoites [28].
  • In contrast, after immunization with multiple doses of irradiated sporozoites, both IFN-gamma R-/- and wild-type mice mounted an immune response, which strongly inhibited the development of liver stage parasites [29].
  • There was significant homology in amino acid sequence between thrombospondin and a conserved region in the circumsporozoite protein of two malarial sporozoites [30].
  • All mice immunized with P. berghei irradiated sporozoites were protected against a sporozoite challenge, including perforin deficient/CD95L mutant animals [31].
  • By Western blot, these antisera reacted with the mycobacterial Hsp65 and recognized a protein of approximately 65 kDa in P. yoelii sporozoites and P. falciparum blood stages [32].

Analytical, diagnostic and therapeutic context of Sporozoites


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  2. Impregnated bed nets for malaria control: biological success and social responsibility. Sexton, J.D. Am. J. Trop. Med. Hyg. (1994) [Pubmed]
  3. Interferon-gamma-independent CD8+ T cell-mediated protective anti-malaria immunity elicited by recombinant adenovirus. Rodrigues, E.G., Claassen, J., Lee, S., Wilson, J.M., Nussenzweig, R.S., Tsuji, M. Parasite Immunol. (2000) [Pubmed]
  4. Production in ascites fluid of biosynthetically labelled monoclonal antibody to Theileria parva sporozoites. Dobbelaere, D.A., Spooner, P.R. J. Immunol. Methods (1985) [Pubmed]
  5. In vitro infectivity of cryopreserved Plasmodium berghei sporozoites to cultured cells. Hollingdale, M.R., Leland, P., Sigler, C.I., Leef, J.L. Trans. R. Soc. Trop. Med. Hyg. (1985) [Pubmed]
  6. A novel Plasmodium falciparum sporozoite and liver stage antigen (SALSA) defines major B, T helper, and CTL epitopes. Bottius, E., BenMohamed, L., Brahimi, K., Gras, H., Lepers, J.P., Raharimalala, L., Aikawa, M., Meis, J., Slierendregt, B., Tartar, A., Thomas, A., Druilhe, P. J. Immunol. (1996) [Pubmed]
  7. In vitro cultivation of the exoerythrocytic stage of Plasmodium berghei from sporozoites. Hollingdale, M.R., Leef, J.L., McCullough, M., Beaudoin, R.L. Science (1981) [Pubmed]
  8. Sporozoite-induced malaria: therapeutic effects of glycolipids in liposomes. Alving, C.R., Schneider, I., Swartz, G.M., Steck, E.A. Science (1979) [Pubmed]
  9. Dual interaction of the malaria circumsporozoite protein with the low density lipoprotein receptor-related protein (LRP) and heparan sulfate proteoglycans. Shakibaei, M., Frevert, U. J. Exp. Med. (1996) [Pubmed]
  10. Remnant lipoproteins inhibit malaria sporozoite invasion of hepatocytes. Sinnis, P., Willnow, T.E., Briones, M.R., Herz, J., Nussenzweig, V. J. Exp. Med. (1996) [Pubmed]
  11. Plasmodium berghei: reaction of sporozoites with chemically and enzymatically modified hepatoma cells. Pancake, S.J., Hollingdale, M.R. Exp. Parasitol. (1986) [Pubmed]
  12. Observations on early and late post-sporozoite tissue stages in primate malaria. V. The effect of pyrimethamine and proguanil upon tissue hypnozoites and schizonts of Plasmodium cynomolgi bastianellii. Jiang, J.B., Bray, R.S., Krotoski, W.A., Canning, E.U., Liang, D.S., Huang, J.C., Liao, J.Y., Li, D.S., Lun, Z.R., Landau, I., Krotowski, W.A. Trans. R. Soc. Trop. Med. Hyg. (1988) [Pubmed]
  13. Efficacy of oral sulfadimethoxine against two gregarine parasites, Protomagalhaensia granulosae and Gregarina cubensis (Apicomplexa: Eugregarinida), infecting the Death's Head cockroach, Blaberus discoidalis. Clopton, R.E., Smith, A. J. Parasitol. (2002) [Pubmed]
  14. Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells. Frevert, U., Galinski, M.R., Hügel, F.U., Allon, N., Schreier, H., Smulevitch, S., Shakibaei, M., Clavijo, P. EMBO J. (1998) [Pubmed]
  15. Immunity to Plasmodium falciparum malaria sporozoites by somatic transgene immunization. Gerloni, M., Baliou, W.R., Billetta, R., Zanetti, M. Nat. Biotechnol. (1997) [Pubmed]
  16. A recombinant sporozoite surface antigen of Theileria parva induces protection in cattle. Musoke, A., Morzaria, S., Nkonge, C., Jones, E., Nene, V. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  17. Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. van Dijk, M.R., Douradinha, B., Franke-Fayard, B., Heussler, V., van Dooren, M.W., van Schaijk, B., van Gemert, G.J., Sauerwein, R.W., Mota, M.M., Waters, A.P., Janse, C.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  18. Malaria sporozoites actively enter and pass through rat Kupffer cells prior to hepatocyte invasion. Pradel, G., Frevert, U. Hepatology (2001) [Pubmed]
  19. Mannose-binding lectin is a component of innate mucosal defense against Cryptosporidium parvum in AIDS. Kelly, P., Jack, D.L., Naeem, A., Mandanda, B., Pollok, R.C., Klein, N.J., Turner, M.W., Farthing, M.J. Gastroenterology (2000) [Pubmed]
  20. The A-domain and the thrombospondin-related motif of Plasmodium falciparum TRAP are implicated in the invasion process of mosquito salivary glands. Wengelnik, K., Spaccapelo, R., Naitza, S., Robson, K.J., Janse, C.J., Bistoni, F., Waters, A.P., Crisanti, A. EMBO J. (1999) [Pubmed]
  21. Recombinant viruses expressing a human malaria antigen can elicit potentially protective immune CD8+ responses in mice. Miyahira, Y., García-Sastre, A., Rodriguez, D., Rodriguez, J.R., Murata, K., Tsuji, M., Palese, P., Esteban, M., Zavala, F., Nussenzweig, R.S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  22. IL-12 and NK cells are required for antigen-specific adaptive immunity against malaria initiated by CD8+ T cells in the Plasmodium yoelii model. Doolan, D.L., Hoffman, S.L. J. Immunol. (1999) [Pubmed]
  23. Tick salivary gland extract and interleukin-2 stimulation enhance susceptibility of lymphocytes to infection by Theileria parva sporozoites. Shaw, M.K., Tilney, L.G., McKeever, D.J. Infect. Immun. (1993) [Pubmed]
  24. Malaria sporozoites and circumsporozoite proteins bind specifically to sulfated glycoconjugates. Pancake, S.J., Holt, G.D., Mellouk, S., Hoffman, S.L. J. Cell Biol. (1992) [Pubmed]
  25. Protective T cell immunity against malaria liver stage after vaccination with live sporozoites under chloroquine treatment. Belnoue, E., Costa, F.T., Frankenberg, T., Vigário, A.M., Voza, T., Leroy, N., Rodrigues, M.M., Landau, I., Snounou, G., Rénia, L. J. Immunol. (2004) [Pubmed]
  26. Protective monoclonal antibody defines a circumsporozoite-like glycoprotein exoantigen of Cryptosporidium parvum sporozoites and merozoites. Riggs, M.W., Stone, A.L., Yount, P.A., Langer, R.C., Arrowood, M.J., Bentley, D.L. J. Immunol. (1997) [Pubmed]
  27. Conserved group-specific epitopes of the circumsporozoite proteins revealed by antibodies to synthetic peptides. Vergara, U., Ruiz, A., Ferreira, A., Nussenzweig, R.S., Nussenzweig, V. J. Immunol. (1985) [Pubmed]
  28. Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells. Seguin, M.C., Klotz, F.W., Schneider, I., Weir, J.P., Goodbary, M., Slayter, M., Raney, J.J., Aniagolu, J.U., Green, S.J. J. Exp. Med. (1994) [Pubmed]
  29. Development of antimalaria immunity in mice lacking IFN-gamma receptor. Tsuji, M., Miyahira, Y., Nussenzweig, R.S., Aguet, M., Reichel, M., Zavala, F. J. Immunol. (1995) [Pubmed]
  30. Partial amino acid sequence of human thrombospondin as determined by analysis of cDNA clones: homology to malarial circumsporozoite proteins. Kobayashi, S., Eden-McCutchan, F., Framson, P., Bornstein, P. Biochemistry (1986) [Pubmed]
  31. Elimination of P. berghei liver stages is independent of Fas (CD95/Apo-I) or perforin-mediated cytotoxicity. Renggli, J., Hahne, M., Matile, H., Betschart, B., Tschopp, J., Corradin, G. Parasite Immunol. (1997) [Pubmed]
  32. Plasmodium yoelii: cloning and characterization of the gene encoding for the mitochondrial heat shock protein 60. Sanchez, G.I., Carucci, D.J., Sacci, J., Resau, J.H., Rogers, W.O., Kumar, N., Hoffman, S.L. Exp. Parasitol. (1999) [Pubmed]
  33. Neutralization-sensitive epitopes are exposed on the surface of infectious Cryptosporidium parvum sporozoites. Riggs, M.W., McGuire, T.C., Mason, P.H., Perryman, L.E. J. Immunol. (1989) [Pubmed]
  34. Levels of antibodies to Plasmodium falciparum sporozoite surface antigens reflect malaria transmission rates and are persistent in the absence of reinfection. Druilhe, P., Pradier, O., Marc, J.P., Miltgen, F., Mazier, D., Parent, G. Infect. Immun. (1986) [Pubmed]
  35. Induction of cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein by immunization with soluble recombinant protein without adjuvant. Malik, A., Gross, M., Ulrich, T., Hoffman, S.L. Infect. Immun. (1993) [Pubmed]
  36. Immunogenicity of Plasmodium falciparum and Plasmodium vivax circumsporozoite protein repeat multiple antigen constructs (MAC). Udhayakumar, V., Saekhou, A., Fang, S., Jue, D., Wohlhueter, R.M., Lal, A.A. Vaccine (1998) [Pubmed]
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