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ANTIGENIC DIVERSITY IN MAXADILAN, A SALIVARY PROTEIN FROM THE SAND FLY VECTOR OF AMERICAN VISCERAL LEISHMANIASIS

The salivary protein maxadilan (MAX) is a vasodilator and immunomodulator from the sand fly vector of the protozoan parasite Leishmania chagasi. Vaccinating BALB/c mice with sand fly salivary gland extracts or with MAX protects the host against L. major infection. Because of the potential use of MAX in an anti-Leishmania vaccine, we characterized the vertebrate host IgG response to MAX in the present study. Our immunochemical analysis indicated that antibodies to MAX were detected in BALB/c mice, as well as in pigs and humans, from a area in Nicaragua endemic for Lutzomyia longipalpis. Previous studies demonstrate that the MAX protein is polymorphic on the amino acid level. Our findings suggested that naturally occurring MAX variants were recognized specifically by the host immune system and antigenicity appeared to be associated with amino-acid sequence variability. Thus, antigenic diversity of MAX and possibly of other arthropod salivary proteins may dictate the development of vector-based vaccines(s).

Received May 14, 2002. Accepted for publication March 3, 2003.

Acknowledgments: We thank Drs. Daniel Freeman and Frederic Tripet for discussing the statistical applications used in the manuscript, Dr. Dia Elnaiem for thoughtful comments, Dr. Richard Titus for his gift of synthetic MAX, Dr. Eva Harris for the human sera from Nicaragua, and Drs. José Ribeiro and Barbara Doughty for their critical reading of the manuscript and supply of essential reagents.

Financial support: This work was funded by National Institutes of Health (grants T32 AI-075261 and AI-39540).

^* These authors contributed equally to this paper.

Authors’ addresses: Rania S. Milleron, John-Paul Mutebi, Huaizhi Yin, and Lynn Soong, Department of Pathology and World Health Organization Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609. Sonia Valle and Alberto Montoya, Departamentos de Entomologia y Parasitologia, Centro Nacional de Diagnostico y Referencia, Ministerio de Salud, Managua, Nicaragua. Gregory C. Lanzaro, Department of Entomology, University of California, Davis, CA 95616-8579, Telephone: 530-752-5833, Fax: 530-752-1537, E-mail: gclanzaro{at}ucdavis.edu.

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