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Infection and Immunity, February 2002, p. 851-858, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.851-858.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Onchocerca volvulus Glycolytic Enzyme Fructose-1,6-Bisphosphate Aldolase as a Target for a Protective Immune Response in Humans

James S. McCarthy,1,2* Moira Wieseman,2 Joe Tropea,2 David Kaslow,2 David Abraham,3 Sara Lustigman,4 Rocky Tuan,5 Ronald H. Guderian,6 and Thomas B. Nutman2

University of Western Australia, Department of Medicine, Fremantle Hospital, Fremantle, Western Australia, Australia,1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,2 Department of Microbiology and Immunology,3 Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021,4 Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,5 Investigaciones Clinicas, Hospital Vozandes, Quito, Ecuador6

Received 16 March 2001/ Returned for modification 18 May 2001/ Accepted 12 October 2001

To identify potential vaccine candidates for the prevention of infection with the filarial nematode Onchocerca volvulus, we screened an O. volvulus L3 stage cDNA library with sera from putatively immune (PI) subjects, and a prominent immunogenic clone of 1,184 nucleotides was identified. It contained an open reading frame of 363 amino acids encoding the glycolytic enzyme fructose 1,6 bisphosphate aldolase (Ov-fba-1). Immunolocalization experiments demonstrated that the protein was most abundantly expressed in metabolically active tissues, including body wall muscle and the reproductive tract of adult female worms. Immunoelectron microscopy of L3 demonstrated binding in the region where the cuticle separates during molting, in the channels connecting the esophagus to the cuticle, and in the basal lamina surrounding the esophagus and the body cavity. Among subjects from areas where this organism is endemic specific humoral and cellular immune responses to recombinant protein were observed in both PI and infected subjects, whereas responses were not observed among subjects who had not been exposed to O. volvulus. Despite the absence of differential responsiveness in parasite-exposed human populations, when the recombinant was tested for protective efficacy in a mouse chamber model, a reduction in survival of larvae by ca. 50% was seen. This observation provides support for the further study of this parasite enzyme as a vaccine candidate in larger animal models.

* Corresponding author. Mailing address: University Department of Medicine, Fremantle Hospital, Fremantle, Western Australia 6959, Australia. Phone: 61-8-9431-3233. Fax: 61-8-9431-2977. E-mail: james.mccarthy{at}uwa.edu.au.

Editor: J. M. Mansfield

Infection and Immunity, February 2002, p. 851-858, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.2.851-858.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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