title: Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals.
abstract: The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.
authors.affiliation: Department of Microbiology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA. jeff@cpqrr.fiocruz.br
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bethony
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.forename: Michael
authors.initials: M
authors.lastname: Smout
authors.forename: Simon
authors.initials: S
authors.lastname: Brooker
authors.forename: Susana
authors.initials: S
authors.lastname: Mendez
authors.forename: Jordan
authors.initials: J
authors.lastname: Plieskatt
authors.forename: Gaddam
authors.initials: G
authors.lastname: Goud
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Bottazzi
authors.forename: Bin
authors.initials: B
authors.lastname: Zhan
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Angela
authors.initials: A
authors.lastname: Williamson
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xiao
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000722:Ancylostoma / Q000472:pathogenicity*; D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D004947:Esophagus / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology; D015801:Helminth Proteins / Q000737:chemistry*; D006725:Hookworm Infections / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D017221:Necator americanus / Q000472:pathogenicity*; D011994:Recombinant Proteins / Q000737:chemistry; D012044:Regression Analysis; D013997:Time Factors; D014612:Vaccines
chemical_list: C483967:ASP-1 protein, Ancylostoma ceylanicum; C508387:ASP-1 protein, Necator americanus; C483968:ASP-2 protein, Ancylostoma ceylanicum; D000947:Antigens, Helminth; D015801:Helminth Proteins; D011994:Recombinant Proteins; D014612:Vaccines