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Infection and Immunity, June 2001, p. 3845-3852, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3845-3952.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Antibodies against Plasmodium falciparum Liver-Stage Antigen 3 Cross-React with Plasmodium yoelii Preerythrocytic-Stage Epitopes and Inhibit Sporozoite Invasion In Vitro and In Vivo

Karima Brahimi, Edgar Badell, Jean-Pierre Sauzet, Lbachir BenMohamed, Pierre Daubersies, Claudine Guérin-Marchand, George Snounou, and Pierre Druilhe*

Laboratoire de Parasitologie Biomédicale, Institut Pasteur, 75015 Paris Cedex 15, France

Received 6 December 2000/Returned for modification 29 January 2001/Accepted 26 March 2001

The Plasmodium falciparum liver-stage antigen 3 (LSA3), a recently identified preerythrocytic antigen, induces protection against malaria in chimpanzees. Using antibodies from individuals with hyperimmunity to malaria affinity purified on recombinant or synthetic polypeptides of LSA3, we identified four non-cross-reactive B-cell epitopes in Plasmodium yoelii preerythrocytic stages. On sporozoites the P. yoelii protein detected has a molecular mass similar to that of LSA3. T-cell epitopes cross-reacting with P. yoelii were also demonstrated using peripheral blood lymphocytes from LSA3-immunized chimpanzees. In contrast, no cross-reactive epitopes were found in Plasmodium berghei. LSA3-specific human antibodies exerted up to 100% inhibition of in vitro invasion of P. yoelii sporozoites into mouse hepatocytes. This strong in vitro activity was reproduced in vivo by passive transfer of LSA3 antibodies. These results indicate that the homologous epitopes may be biologically functional and suggest that P. yoelii could be used as a model to assess the antisporozoite activity of anti-LSA3 antibodies.

* Corresponding author. Mailing address: Bio-Medical Parasitology Unit, Institut Pasteur, 28, rue du Docteur Roux, 75015 Paris, France. Phone: 33-1-45 68 85 78. Fax: 33-1-45 68 86 40. E-mail: druilhe{at}pasteur.fr.

Infection and Immunity, June 2001, p. 3845-3852, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3845-3952.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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