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. 1990 May;87(10):4017–4021. doi: 10.1073/pnas.87.10.4017

Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins.

S Herrera 1, M A Herrera 1, B L Perlaza 1, Y Burki 1, P Caspers 1, H Döbeli 1, D Rotmann 1, U Certa 1
PMCID: PMC54035  PMID: 2187200

Abstract

The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen preparations could protect susceptible monkeys from an otherwise lethal malaria infection. In contrast to the natural antigen, recombinant p41 protein (P. falciparum aldolase) could not protect monkeys, although all animals seroconverted. 190N antigen, a recombinant protein containing conserved sequences of the major merozoite surface antigen p190, protected two of five monkeys from critical levels of infection with the highly virulent FVO isolate of P. falciparum. However, the B- and T-cell responses to 190N antigen were similar in protected and unprotected animals so that other unknown factors may contribute to protection. Higher purity or lack of protective epitopes or different structure of protective epitopes in the recombinant proteins might explain the better performance of parasite-derived antigens in vaccination trials. The partial protection obtained with 190N antigen suggests that this molecule could contribute to a vaccine mixture against P. falciparum.

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Selected References

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

  1. Certa U., Bannwarth W., Stüber D., Gentz R., Lanzer M., Le Grice S., Guillot F., Wendler I., Hunsmann G., Bujard H. Subregions of a conserved part of the HIV gp41 transmembrane protein are differentially recognized by antibodies of infected individuals. EMBO J. 1986 Nov;5(11):3051–3056. doi: 10.1002/j.1460-2075.1986.tb04605.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Certa U., Ghersa P., Döbeli H., Matile H., Kocher H. P., Shrivastava I. K., Shaw A. R., Perrin L. H. Aldolase activity of a Plasmodium falciparum protein with protective properties. Science. 1988 May 20;240(4855):1036–1038. doi: 10.1126/science.3285469. [DOI] [PubMed] [Google Scholar]
  3. Certa U., Rotmann D., Matile H., Reber-Liske R. A naturally occurring gene encoding the major surface antigen precursor p190 of Plasmodium falciparum lacks tripeptide repeats. EMBO J. 1987 Dec 20;6(13):4137–4142. doi: 10.1002/j.1460-2075.1987.tb02759.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gentz R., Certa U., Takacs B., Matile H., Döbeli H., Pink R., Mackay M., Bone N., Scaife J. G. Major surface antigen p190 of Plasmodium falciparum: detection of common epitopes present in a variety of plasmodia isolates. EMBO J. 1988 Jan;7(1):225–230. doi: 10.1002/j.1460-2075.1988.tb02803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Mackay M., Goman M., Bone N., Hyde J. E., Scaife J., Certa U., Stunnenberg H., Bujard H. Polymorphism of the precursor for the major surface antigens of Plasmodium falciparum merozoites: studies at the genetic level. EMBO J. 1985 Dec 30;4(13B):3823–3829. doi: 10.1002/j.1460-2075.1985.tb04154.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Perrin L. H., Merkli B., Gabra M. S., Stocker J. W., Chizzolini C., Richle R. Immunization with a Plasmodium falciparum merozoite surface antigen induces a partial immunity in monkeys. J Clin Invest. 1985 May;75(5):1718–1721. doi: 10.1172/JCI111881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Perrin L. H., Merkli B., Loche M., Chizzolini C., Smart J., Richle R. Antimalarial immunity in Saimiri monkeys. Immunization with surface components of asexual blood stages. J Exp Med. 1984 Aug 1;160(2):441–451. doi: 10.1084/jem.160.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Siddiqui W. A. An effective immunization of experimental monkeys against a human malaria parasite, Plasmodium falciparum. Science. 1977 Jul 22;197(4301):388–389. doi: 10.1126/science.406671. [DOI] [PubMed] [Google Scholar]
  9. Siddiqui W. A., Tam L. Q., Kramer K. J., Hui G. S., Case S. E., Yamaga K. M., Chang S. P., Chan E. B., Kan S. C. Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1987 May;84(9):3014–3018. doi: 10.1073/pnas.84.9.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sinigaglia F., Takacs B., Jacot H., Matile H., Pink J. R., Crisanti A., Bujard H. Nonpolymorphic regions of p190, a protein of the Plasmodium falciparum erythrocytic stage, contain both T and B cell epitopes. J Immunol. 1988 May 15;140(10):3568–3572. [PubMed] [Google Scholar]
  11. Srivastava I. K., Schmidt M., Certa U., Döbeli H., Perrin L. H. Specificity and inhibitory activity of antibodies to Plasmodium falciparum aldolase. J Immunol. 1990 Feb 15;144(4):1497–1503. [PubMed] [Google Scholar]
  12. Tanabe K., Mackay M., Goman M., Scaife J. G. Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum. J Mol Biol. 1987 May 20;195(2):273–287. doi: 10.1016/0022-2836(87)90649-8. [DOI] [PubMed] [Google Scholar]

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