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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 1997 Sep 29;352(1359):1361–1367. doi: 10.1098/rstb.1997.0121

Pre-erythrocytic-stage immune effector mechanisms in Plasmodium spp. infections.

D L Doolan 1, S L Hoffman 1
PMCID: PMC1692030  PMID: 9355128

Abstract

The potent protective immunity against malaria induced by immunization of mice and humans with radiation-attenuated Plasmodium spp. sporozoites is thought to be mediated primarily by T-cell responses directed against infected hepatocytes. This has led to considerable efforts to develop subunit vaccines that duplicate this protective immunity, but a universally effective vaccine is still not available and in vitro correlates of protective immunity have not been established. Contributing to this delay has been a lack of understanding of the mechanisms responsible for the protection. There are now data indicating that CD8+ T cells, CD4+ T cells, cytokines, and nitric oxide can all mediate the elimination of infected hepatocytes in vitro and in vivo. By dissecting the protection induced by immunization with irradiated sporozoite, DNA and synthetic peptide-adjuvant vaccines, we have demonstrated that different T-cell-dependent immune responses mediate protective immunity in the same inbred strain of mouse, depending on the method of immunization. Furthermore, the mechanism of protection induced by a single method of immunization may vary among different strains of mice. These data have important implications for the development of pre-erythrocytic-stage vaccines designed to protect a heterogeneous human population, and of assays that predict protective immunity.

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Selected References

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  1. Aggarwal A., Kumar S., Jaffe R., Hone D., Gross M., Sadoff J. Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. J Exp Med. 1990 Oct 1;172(4):1083–1090. doi: 10.1084/jem.172.4.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alonso P. L., Lindsay S. W., Armstrong J. R., Conteh M., Hill A. G., David P. H., Fegan G., de Francisco A., Hall A. J., Shenton F. C. The effect of insecticide-treated bed nets on mortality of Gambian children. Lancet. 1991 Jun 22;337(8756):1499–1502. doi: 10.1016/0140-6736(91)93194-e. [DOI] [PubMed] [Google Scholar]
  3. Beadle C., McElroy P. D., Oster C. N., Beier J. C., Oloo A. J., Onyango F. K., Chumo D. K., Bales J. D., Sherwood J. A., Hoffman S. L. Impact of transmission intensity and age on Plasmodium falciparum density and associated fever: implications for malaria vaccine trial design. J Infect Dis. 1995 Oct;172(4):1047–1054. doi: 10.1093/infdis/172.4.1047. [DOI] [PubMed] [Google Scholar]
  4. Bouharoun-Tayoun H., Attanath P., Sabchareon A., Chongsuphajaisiddhi T., Druilhe P. Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med. 1990 Dec 1;172(6):1633–1641. doi: 10.1084/jem.172.6.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. COHEN S., McGREGOR I. A., CARRINGTON S. Gamma-globulin and acquired immunity to human malaria. Nature. 1961 Nov 25;192:733–737. doi: 10.1038/192733a0. [DOI] [PubMed] [Google Scholar]
  6. Charoenvit Y., Collins W. E., Jones T. R., Millet P., Yuan L., Campbell G. H., Beaudoin R. L., Broderson J. R., Hoffman S. L. Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence. Science. 1991 Feb 8;251(4994):668–671. doi: 10.1126/science.1704150. [DOI] [PubMed] [Google Scholar]
  7. Charoenvit Y., Mellouk S., Cole C., Bechara R., Leef M. F., Sedegah M., Yuan L. F., Robey F. A., Beaudoin R. L., Hoffman S. L. Monoclonal, but not polyclonal, antibodies protect against Plasmodium yoelii sporozoites. J Immunol. 1991 Feb 1;146(3):1020–1025. [PubMed] [Google Scholar]
  8. Charoenvit Y., Mellouk S., Sedegah M., Toyoshima T., Leef M. F., De la Vega P., Beaudoin R. L., Aikawa M., Fallarme V., Hoffman S. L. Plasmodium yoelii: 17-kDa hepatic and erythrocytic stage protein is the target of an inhibitory monoclonal antibody. Exp Parasitol. 1995 May;80(3):419–429. doi: 10.1006/expr.1995.1054. [DOI] [PubMed] [Google Scholar]
  9. Chen D. H., Tigelaar R. E., Weinbaum F. I. Immunity to sporozoite-induced malaria infeciton in mice. I. The effect of immunization of T and B cell-deficient mice. J Immunol. 1977 Apr;118(4):1322–1327. [PubMed] [Google Scholar]
  10. Clyde D. F., McCarthy V. C., Miller R. M., Hornick R. B. Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am J Med Sci. 1973 Dec;266(6):398–403. doi: 10.1097/00000441-197312000-00001. [DOI] [PubMed] [Google Scholar]
  11. Clyde D. F., Most H., McCarthy V. C., Vanderberg J. P. Immunization of man against sporozite-induced falciparum malaria. Am J Med Sci. 1973 Sep;266(3):169–177. doi: 10.1097/00000441-197309000-00002. [DOI] [PubMed] [Google Scholar]
  12. Cochrane A. H., Santoro F., Nussenzweig V., Gwadz R. W., Nussenzweig R. S. Monoclonal antibodies identify the protective antigens of sporozoites of Plasmodium knowlesi. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5651–5655. doi: 10.1073/pnas.79.18.5651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Doolan D. L., Hoffman S. L. Multi-gene vaccination against malaria: A multistage, multi-immune response approach. Parasitol Today. 1997 May;13(5):171–178. doi: 10.1016/s0169-4758(97)01040-5. [DOI] [PubMed] [Google Scholar]
  14. Doolan D. L., Sedegah M., Hedstrom R. C., Hobart P., Charoenvit Y., Hoffman S. L. Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity. J Exp Med. 1996 Apr 1;183(4):1739–1746. doi: 10.1084/jem.183.4.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Edelman R., Hoffman S. L., Davis J. R., Beier M., Sztein M. B., Losonsky G., Herrington D. A., Eddy H. A., Hollingdale M. R., Gordon D. M. Long-term persistence of sterile immunity in a volunteer immunized with X-irradiated Plasmodium falciparum sporozoites. J Infect Dis. 1993 Oct;168(4):1066–1070. doi: 10.1093/infdis/168.4.1066. [DOI] [PubMed] [Google Scholar]
  16. Egan J. E., Hoffman S. L., Haynes J. D., Sadoff J. C., Schneider I., Grau G. E., Hollingdale M. R., Ballou W. R., Gordon D. M. Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 1993 Aug;49(2):166–173. doi: 10.4269/ajtmh.1993.49.166. [DOI] [PubMed] [Google Scholar]
  17. Egan J. E., Weber J. L., Ballou W. R., Hollingdale M. R., Majarian W. R., Gordon D. M., Maloy W. L., Hoffman S. L., Wirtz R. A., Schneider I. Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development. Science. 1987 Apr 24;236(4800):453–456. doi: 10.1126/science.3551073. [DOI] [PubMed] [Google Scholar]
  18. Ferreira A., Schofield L., Enea V., Schellekens H., van der Meide P., Collins W. E., Nussenzweig R. S., Nussenzweig V. Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. Science. 1986 May 16;232(4752):881–884. doi: 10.1126/science.3085218. [DOI] [PubMed] [Google Scholar]
  19. Flynn J. L., Weiss W. R., Norris K. A., Seifert H. S., Kumar S., So M. Generation of a cytotoxic T-lymphocyte response using a Salmonella antigen-delivery system. Mol Microbiol. 1990 Dec;4(12):2111–2118. doi: 10.1111/j.1365-2958.1990.tb00572.x. [DOI] [PubMed] [Google Scholar]
  20. Gwadz R. W., Cochrane A. H., Nussenzweig V., Nussenzweig R. S. Preliminary studies on vaccination of rhesus monkeys with irradiated sporozoites of Plasmodium knowlesi and characterization of surface antigens of these parasites. Bull World Health Organ. 1979;57 (Suppl 1):165–173. [PMC free article] [PubMed] [Google Scholar]
  21. HUFF C. G., MARCHBANK D. F., SHIROISHI T. Changes in infectiousness of malarial gametocytes. II. Analysis of the possible causative factors. Exp Parasitol. 1958 Jul;7(4):399–417. doi: 10.1016/0014-4894(58)90036-5. [DOI] [PubMed] [Google Scholar]
  22. Herrington D. A., Nardin E. H., Losonsky G., Bathurst I. C., Barr P. J., Hollingdale M. R., Edelman R., Levine M. M. Safety and immunogenicity of a recombinant sporozoite malaria vaccine against Plasmodium vivax. Am J Trop Med Hyg. 1991 Dec;45(6):695–701. doi: 10.4269/ajtmh.1991.45.695. [DOI] [PubMed] [Google Scholar]
  23. Hoffman S. L., Crutcher J. M., Puri S. K., Ansari A. A., Villinger F., Franke E. D., Singh P. P., Finkelman F., Gately M. K., Dutta G. P. Sterile protection of monkeys against malaria after administration of interleukin-12. Nat Med. 1997 Jan;3(1):80–83. doi: 10.1038/nm0197-80. [DOI] [PubMed] [Google Scholar]
  24. Hoffman S. L., Isenbarger D., Long G. W., Sedegah M., Szarfman A., Waters L., Hollingdale M. R., van der Meide P. H., Finbloom D. S., Ballou W. R. Sporozoite vaccine induces genetically restricted T cell elimination of malaria from hepatocytes. Science. 1989 Jun 2;244(4908):1078–1081. doi: 10.1126/science.2524877. [DOI] [PubMed] [Google Scholar]
  25. Hoffman S. L., Weiss W., Mellouk S., Sedegah M. Irradiated sporozoite vaccine induces cytotoxic T lymphocytes that recognize malaria antigens on the surface of infected hepatocytes. Immunol Lett. 1990 Aug;25(1-3):33–38. doi: 10.1016/0165-2478(90)90087-7. [DOI] [PubMed] [Google Scholar]
  26. Hollingdale M. R., Nardin E. H., Tharavanij S., Schwartz A. L., Nussenzweig R. S. Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J Immunol. 1984 Feb;132(2):909–913. [PubMed] [Google Scholar]
  27. Khusmith S., Charoenvit Y., Kumar S., Sedegah M., Beaudoin R. L., Hoffman S. L. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science. 1991 May 3;252(5006):715–718. doi: 10.1126/science.1827210. [DOI] [PubMed] [Google Scholar]
  28. Khusmith S., Sedegah M., Hoffman S. L. Complete protection against Plasmodium yoelii by adoptive transfer of a CD8+ cytotoxic T-cell clone recognizing sporozoite surface protein 2. Infect Immun. 1994 Jul;62(7):2979–2983. doi: 10.1128/iai.62.7.2979-2983.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Li S., Rodrigues M., Rodriguez D., Rodriguez J. R., Esteban M., Palese P., Nussenzweig R. S., Zavala F. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5214–5218. doi: 10.1073/pnas.90.11.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maheshwari R. K., Czarniecki C. W., Dutta G. P., Puri S. K., Dhawan B. N., Friedman R. M. Recombinant human gamma interferon inhibits simian malaria. Infect Immun. 1986 Sep;53(3):628–630. doi: 10.1128/iai.53.3.628-630.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mazier D., Mellouk S., Beaudoin R. L., Texier B., Druilhe P., Hockmeyer W., Trosper J., Paul C., Charoenvit Y., Young J. Effect of antibodies to recombinant and synthetic peptides on P. falciparum sporozoites in vitro. Science. 1986 Jan 10;231(4734):156–159. doi: 10.1126/science.3510455. [DOI] [PubMed] [Google Scholar]
  32. Mellouk S., Green S. J., Nacy C. A., Hoffman S. L. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol. 1991 Jun 1;146(11):3971–3976. [PubMed] [Google Scholar]
  33. Mellouk S., Hoffman S. L., Liu Z. Z., de la Vega P., Billiar T. R., Nussler A. K. Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin. Infect Immun. 1994 Sep;62(9):4043–4046. doi: 10.1128/iai.62.9.4043-4046.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mellouk S., Maheshwari R. K., Rhodes-Feuillette A., Beaudoin R. L., Berbiguier N., Matile H., Miltgen F., Landau I., Pied S., Chigot J. P. Inhibitory activity of interferons and interleukin 1 on the development of Plasmodium falciparum in human hepatocyte cultures. J Immunol. 1987 Dec 15;139(12):4192–4195. [PubMed] [Google Scholar]
  35. Migliorini P., Betschart B., Corradin G. Malaria vaccine: immunization of mice with a synthetic T cell helper epitope alone leads to protective immunity. Eur J Immunol. 1993 Feb;23(2):582–585. doi: 10.1002/eji.1830230245. [DOI] [PubMed] [Google Scholar]
  36. Mitchell G. H., Butcher G. A., Cohen S. Merozoite vaccination against Plasmodium knowlesi malaria. Immunology. 1975 Aug;29(2):397–407. [PMC free article] [PubMed] [Google Scholar]
  37. Nussenzweig R. S., Vanderberg J. P., Most H., Orton C. Specificity of protective immunity produced by x-irradiated Plasmodium berghei sporozoites. Nature. 1969 May 3;222(5192):488–489. doi: 10.1038/222488a0. [DOI] [PubMed] [Google Scholar]
  38. Nussenzweig V., Nussenzweig R. S. Rationale for the development of an engineered sporozoite malaria vaccine. Adv Immunol. 1989;45:283–334. doi: 10.1016/s0065-2776(08)60695-1. [DOI] [PubMed] [Google Scholar]
  39. Nussler A., Pied S., Goma J., Rénia L., Miltgen F., Grau G. E., Mazier D. TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6. Int Immunol. 1991 Apr;3(4):317–321. doi: 10.1093/intimm/3.4.317. [DOI] [PubMed] [Google Scholar]
  40. Pied S., Civas A., Berlot-Picard F., Renia L., Miltgen F., Gentilini M., Doly J., Mazier D. IL-6 induced by IL-1 inhibits malaria pre-erythrocytic stages but its secretion is down-regulated by the parasite. J Immunol. 1992 Jan 1;148(1):197–201. [PubMed] [Google Scholar]
  41. Potocnjak P., Yoshida N., Nussenzweig R. S., Nussenzweig V. Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J Exp Med. 1980 Jun 1;151(6):1504–1513. doi: 10.1084/jem.151.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rieckmann K. H., Beaudoin R. L., Cassells J. S., Sell K. W. Use of attenuated sporozoites in the immunization of human volunteers against falciparum malaria. Bull World Health Organ. 1979;57 (Suppl 1):261–265. [PMC free article] [PubMed] [Google Scholar]
  43. Rieckmann K. H., Carson P. E., Beaudoin R. L., Cassells J. S., Sell K. W. Letter: Sporozoite induced immunity in man against an Ethiopian strain of Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1974;68(3):258–259. doi: 10.1016/0035-9203(74)90129-1. [DOI] [PubMed] [Google Scholar]
  44. Rodrigues M. M., Cordey A. S., Arreaza G., Corradin G., Romero P., Maryanski J. L., Nussenzweig R. S., Zavala F. CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. Int Immunol. 1991 Jun;3(6):579–585. doi: 10.1093/intimm/3.6.579. [DOI] [PubMed] [Google Scholar]
  45. Rodrigues M., Li S., Murata K., Rodriguez D., Rodriguez J. R., Bacik I., Bennink J. R., Yewdell J. W., Garcia-Sastre A., Nussenzweig R. S. Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity. J Immunol. 1994 Nov 15;153(10):4636–4648. [PubMed] [Google Scholar]
  46. Romero P., Maryanski J. L., Corradin G., Nussenzweig R. S., Nussenzweig V., Zavala F. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989 Sep 28;341(6240):323–326. doi: 10.1038/341323a0. [DOI] [PubMed] [Google Scholar]
  47. Rénia L., Grillot D., Marussig M., Corradin G., Miltgen F., Lambert P. H., Mazier D., Del Giudice G. Effector functions of circumsporozoite peptide-primed CD4+ T cell clones against Plasmodium yoelii liver stages. J Immunol. 1993 Feb 15;150(4):1471–1478. [PubMed] [Google Scholar]
  48. Rénia L., Marussig M. S., Grillot D., Pied S., Corradin G., Miltgen F., Del Giudice G., Mazier D. In vitro activity of CD4+ and CD8+ T lymphocytes from mice immunized with a synthetic malaria peptide. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7963–7967. doi: 10.1073/pnas.88.18.7963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sabchareon A., Burnouf T., Ouattara D., Attanath P., Bouharoun-Tayoun H., Chantavanich P., Foucault C., Chongsuphajaisiddhi T., Druilhe P. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg. 1991 Sep;45(3):297–308. doi: 10.4269/ajtmh.1991.45.297. [DOI] [PubMed] [Google Scholar]
  50. Sadoff J. C., Ballou W. R., Baron L. S., Majarian W. R., Brey R. N., Hockmeyer W. T., Young J. F., Cryz S. J., Ou J., Lowell G. H. Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science. 1988 Apr 15;240(4850):336–338. doi: 10.1126/science.3281260. [DOI] [PubMed] [Google Scholar]
  51. Satchidanandam V., Zavala F., Moss B. Studies using a recombinant vaccinia virus expressing the circumsporozoite protein of Plasmodium berghei. Mol Biochem Parasitol. 1991 Sep;48(1):89–99. doi: 10.1016/0166-6851(91)90167-5. [DOI] [PubMed] [Google Scholar]
  52. Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
  53. Sedegah M., Beaudoin R. L., Majarian W. R., Cochran M. D., Chiang C. H., Sadoff J., Aggarwal A., Charoenvit Y., Hoffman S. L. Evaluation of vaccines designed to induce protective cellular immunity against the Plasmodium yoelii circumsporozoite protein: vaccinia, pseudorabies, and Salmonella transformed with circumsporozoite gene. Bull World Health Organ. 1990;68 (Suppl):109–114. [PMC free article] [PubMed] [Google Scholar]
  54. Sedegah M., Chiang C. H., Weiss W. R., Mellouk S., Cochran M. D., Houghten R. A., Beaudoin R. L., Smith D., Hoffman S. L. Recombinant pseudorabies virus carrying a plasmodium gene: herpesvirus as a new live viral vector for inducing T- and B-cell immunity. Vaccine. 1992;10(9):578–584. doi: 10.1016/0264-410x(92)90436-n. [DOI] [PubMed] [Google Scholar]
  55. Sedegah M., Finkelman F., Hoffman S. L. Interleukin 12 induction of interferon gamma-dependent protection against malaria. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10700–10702. doi: 10.1073/pnas.91.22.10700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sedegah M., Hedstrom R., Hobart P., Hoffman S. L. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9866–9870. doi: 10.1073/pnas.91.21.9866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Stoute J. A., Slaoui M., Heppner D. G., Momin P., Kester K. E., Desmons P., Wellde B. T., Garçon N., Krzych U., Marchand M. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group. N Engl J Med. 1997 Jan 9;336(2):86–91. doi: 10.1056/NEJM199701093360202. [DOI] [PubMed] [Google Scholar]
  58. Tsuji M., Romero P., Nussenzweig R. S., Zavala F. CD4+ cytolytic T cell clone confers protection against murine malaria. J Exp Med. 1990 Nov 1;172(5):1353–1357. doi: 10.1084/jem.172.5.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Verhave J. P., Meuwissen J. H., Golenser J. Cell-mediated reactions and protection after immunization with sporozoites. Isr J Med Sci. 1978 May;14(5):611–616. [PubMed] [Google Scholar]
  60. Wang R., Charoenvit Y., Corradin G., De La Vega P., Franke E. D., Hoffman S. L. Protection against malaria by Plasmodium yoelii sporozoite surface protein 2 linear peptide induction of CD4+ T cell- and IFN-gamma-dependent elimination of infected hepatocytes. J Immunol. 1996 Nov 1;157(9):4061–4067. [PubMed] [Google Scholar]
  61. Wang R., Charoenvit Y., Corradin G., Porrozzi R., Hunter R. L., Glenn G., Alving C. R., Church P., Hoffman S. L. Induction of protective polyclonal antibodies by immunization with a Plasmodium yoelii circumsporozoite protein multiple antigen peptide vaccine. J Immunol. 1995 Mar 15;154(6):2784–2793. [PubMed] [Google Scholar]
  62. Weiss W. R., Berzofsky J. A., Houghten R. A., Sedegah M., Hollindale M., Hoffman S. L. A T cell clone directed at the circumsporozoite protein which protects mice against both Plasmodium yoelii and Plasmodium berghei. J Immunol. 1992 Sep 15;149(6):2103–2109. [PubMed] [Google Scholar]
  63. Weiss W. R., Mellouk S., Houghten R. A., Sedegah M., Kumar S., Good M. F., Berzofsky J. A., Miller L. H., Hoffman S. L. Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J Exp Med. 1990 Mar 1;171(3):763–773. doi: 10.1084/jem.171.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Weiss W. R., Sedegah M., Beaudoin R. L., Miller L. H., Good M. F. CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988 Jan;85(2):573–576. doi: 10.1073/pnas.85.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Yoshida N., Nussenzweig R. S., Potocnjak P., Nussenzweig V., Aikawa M. Hybridoma produces protective antibodies directed against the sporozoite stage of malaria parasite. Science. 1980 Jan 4;207(4426):71–73. doi: 10.1126/science.6985745. [DOI] [PubMed] [Google Scholar]

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