Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1993 Sep;80(1):1–5.

The relative contribution of antibodies, CD4+ and CD8+ T cells to sporozoite-induced protection against malaria.

M Rodrigues 1, R S Nussenzweig 1, F Zavala 1
PMCID: PMC1422124  PMID: 7902331

Abstract

Protective immunity against Plasmodium yoelii, induced by sporozoite immunization, was investigated using a quantitative method based on the measurement of plasmodial ribosomal RNA in the liver of sporozoite-challenged mice. The relative importance of the different immune mechanisms induced by sporozoite immunization was determined by evaluating quantitatively the anti-parasite activity of antibodies, CD4+ and CD8+ T cells. The role of antibodies was determined by passive transfer of immune sera to naive mice. The transfer to mice of sera obtained after a single immunizing dose reduced the liver stages by 47%. The respective contribution of CD4+ and CD8+ T-cell subsets was determined in B10 (H-2b) mice, treated with a monoclonal antibody (mAb) which inhibits B-cell maturation, and subsequently immunized once with irradiated sporozoites. These mice produced low levels of anti-sporozoite antibodies, but were capable of inhibiting the development of liver stages as efficiently as non-manipulated immunized mice. Administration of either anti-CD4 or anti-CD8 mAb to these mice, did not significantly decrease their capacity to inhibit the development of liver stages. We only observed a significant loss of immunity when the mice were depleted in vivo of both CD4+ and CD8+ T cells. In contrast to earlier studies, we found that the induction of protective immunity is not a phenomenon restricted to a few strains of mice having a particular genetic make-up. The apparent non-responsiveness observed in some strains of mice can be overcome by using larger immunizing doses.

Full text

PDF
1

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arreaza G., Corredor V., Zavala F. Plasmodium yoelii: quantification of the exoerythrocytic stages based on the use of ribosomal RNA probes. Exp Parasitol. 1991 Jan;72(1):103–105. doi: 10.1016/0014-4894(91)90127-i. [DOI] [PubMed] [Google Scholar]
  2. Charoenvit Y., Leef M. F., Yuan L. F., Sedegah M., Beaudoin R. L. Characterization of Plasmodium yoelii monoclonal antibodies directed against stage-specific sporozoite antigens. Infect Immun. 1987 Mar;55(3):604–608. doi: 10.1128/iai.55.3.604-608.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Herrington D., Davis J., Nardin E., Beier M., Cortese J., Eddy H., Losonsky G., Hollingdale M., Sztein M., Levine M. Successful immunization of humans with irradiated malaria sporozoites: humoral and cellular responses of the protected individuals. Am J Trop Med Hyg. 1991 Nov;45(5):539–547. doi: 10.4269/ajtmh.1991.45.539. [DOI] [PubMed] [Google Scholar]
  6. Heyman B., Wiersma E. J., Kinoshita T. In vivo inhibition of the antibody response by a complement receptor-specific monoclonal antibody. J Exp Med. 1990 Aug 1;172(2):665–668. doi: 10.1084/jem.172.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Khan Z. M., Vanderberg J. P. Specific inflammatory cell infiltration of hepatic schizonts in BALB/c mice immunized with attenuated Plasmodium yoelii sporozoites. Int Immunol. 1992 Jul;4(7):711–718. doi: 10.1093/intimm/4.7.711. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Mazier D., Rénia L., Nussler A., Pied S., Marussig M., Goma J., Grillot D., Miltgen F., Drapier J. C., Corradin G. Hepatic phase of malaria is the target of cellular mechanisms induced by the previous and the subsequent stages. A crucial role for liver nonparenchymal cells. Immunol Lett. 1990 Aug;25(1-3):65–70. doi: 10.1016/0165-2478(90)90093-6. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. Schofield L. The circumsporozoite protein of Plasmodium: a mechanism of immune evasion by the malaria parasite? Bull World Health Organ. 1990;68 (Suppl):66–73. [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Tam J. P., Clavijo P., Lu Y. A., Nussenzweig V., Nussenzweig R., Zavala F. Incorporation of T and B epitopes of the circumsporozoite protein in a chemically defined synthetic vaccine against malaria. J Exp Med. 1990 Jan 1;171(1):299–306. doi: 10.1084/jem.171.1.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Weiss W. R., Good M. F., Hollingdale M. R., Miller L. H., Berzofsky J. A. Genetic control of immunity to Plasmodium yoelii sporozoites. J Immunol. 1989 Dec 15;143(12):4263–4266. [PubMed] [Google Scholar]
  20. 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]
  21. Zavala F., Tam J. P., Barr P. J., Romero P. J., Ley V., Nussenzweig R. S., Nussenzweig V. Synthetic peptide vaccine confers protection against murine malaria. J Exp Med. 1987 Nov 1;166(5):1591–1596. doi: 10.1084/jem.166.5.1591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zavala F. The multifactorial character of the protective immunity induced by immunization with sporozoites. Res Immunol. 1991 Oct;142(8):654–658. doi: 10.1016/0923-2494(91)90144-8. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES