1. Neutralizing Antibodies to the Hookworm Hemoglobinase Na-APR-1: Implications for a Multivalent Vaccine against Hookworm Infection and Schistosomiasis.
- Author
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Pearson, Mark S., Pickering, Darren A., Tribolet, Leon, Cooper, Leanne, Mulvenna, Jason, Oliveira, Luciana M., Bethony, Jeffrey M., Hotez, Peter J., and Loukas, Alex
- Subjects
IMMUNOGLOBULINS ,HOOKWORM disease ,SCHISTOSOMIASIS vaccines ,ANTIGENS ,PROTEOLYSIS ,MONOCLONAL antibodies ,PEPTIDES ,ANCYLOSTOMA ,NECATOR americanus ,PROTEASE inhibitors - Abstract
The aspartic protease of Necator americanus, Na-APR-1, is a vaccine antigen that induces antibodies that neutralize hemoglobin proteolysis in the gut of the worm. To define the epitopes recognized by these antibodies, monoclonal antibodies (mAbs) were raised and assessed for neutralizing activity. Three immunoglobulin (Ig) G1 mAbs bound to the intestine of N. americanus and inhibited Na-APR-1 enzymatic activity. Overlapping fragments of Na-APR-1 were expressed, and one (APR-1/5B) was recognized by all 3 mAbs; the epitope was further characterized as AGPKAQVEAIQKY (A
291 Y). This same peptide with a Phe/Tyr303 substitution was recognized by mAbs in APR-1 orthologues from Ancylostoma species hookworms. IgG from humans infected with hookworms did not recognize A291 Y but, rather, recognized the S107 L epitope. APR-1/5B was fused to other helminth vaccine antigens, including Schistosoma mansoni Sm-TSP-2 and N. americanus Na-GST-1; antibodies against both chimeras neutralized the enzymatic activity of Na-APR-1. These findings support the incorporation of Na-APR-1 into a multivalent vaccine against hookworm and/or schistosomiasis. [ABSTRACT FROM AUTHOR]- Published
- 2010
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