Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals.
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.
Bethony
Jeffrey
J
Department of Microbiology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA. jeff@cpqrr.fiocruz.br
Loukas
Alex
A
Smout
Michael
M
Brooker
Simon
S
Mendez
Susana
S
Plieskatt
Jordan
J
Goud
Gaddam
G
Bottazzi
Maria Elena
ME
Zhan
Bin
B
Wang
Yan
Y
Williamson
Angela
A
Lustigman
Sara
S
Correa-Oliveira
Rodrigo
R
Xiao
Shuhua
S
Hotez
Peter J
PJ
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
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