Neutralizing antibodies to the hookworm hemoglobinase Na-APR-1: implications for a multivalent vaccine against hookworm Infection and schistosomiasis
Pearson, Mark S., Pickering, Darren A., Tribolet, Leon, Cooper, Leanne, Mulvenna, Jason, Oliveira, Luciana M., Bethony, Jeffrey M., Hotez, Peter J., and Loukas, Alex (2010) Neutralizing antibodies to the hookworm hemoglobinase Na-APR-1: implications for a multivalent vaccine against hookworm Infection and schistosomiasis. Journal of Infectious Diseases, 201 (10). pp. 1561-1569.
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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 (A291Y). 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 A291Y but, rather, recognized the S107L 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.
|Item Type:||Article (Refereed Research - C1)|
|Date Deposited:||09 May 2011 22:17|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%|
|Citation Count from Web of Science||