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Infection and Immunity, June 2004, p. 3604-3608, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3604-3608.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

Peter Preiser ,1,{dagger},{ddagger} Laurent Rénia,2,{dagger} Naresh Singh,3 Bharath Balu,3 William Jarra,1 Tatiana Voza,4 Osamu Kaneko,5 Peter Blair,3 Motomi Torii,5 Irène Landau,4 and John H. Adams3*

Division of Parasitology, National Institute for Medical Research, London, United Kingdom,1 Département d'Immunologie, Institut Cochin, INSERM U567, CNRS 8104, Université René Descartes, Hôpital Cochin,2 Muséum National d'Histoire Naturelle, Parasitologie Comparée et Modèles Expérimentaux, Associés à l'NSERM U567, Paris, France,4 Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana,3 Department of Molecular Parasitology, Ehime University School of Medicine, Shigenobu-cho, Ehime, Japan5

Received 23 December 2003/ Returned for modification 27 January 2004/ Accepted 1 March 2004

MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.

* Corresponding author. Mailing address: Departments of Biological Science, University of Notre Dame, P. O. Box 369, Notre Dame, IN 46556-0369. Phone: (574) 631-8676. Fax: (574) 631-7413. E-mail: jadams3{at}nd.edu.

Editor: W. A. Petri, Jr.

{dagger} P. Preiser and L. Rénia contributed equally to this work.

{ddagger} Present address: Nanyang Technological University, School of Biological Sciences, Singapore 637616, Republic of Singapore.

Infection and Immunity, June 2004, p. 3604-3608, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3604-3608.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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