Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: implications for the development of vaccines against helminths.
BACKGROUND
Necator americanus Ancylostoma-secreted protein 2 (Na-ASP-2) is secreted by infective hookworm larvae on entry into human hosts. Vaccination of laboratory animals with recombinant Na-ASP-2 provides significant protection against challenge infections. In endemic areas antibodies to Na-ASP-2 are associated with reduced risk of heavy N americanus infections.


OBJECTIVE
To assess the safety and immunogenicity of recombinant Na-ASP-2 adjuvanted with Alhydrogel in healthy Brazilian adults previously infected with N americanus.


METHODS
Participants were randomized to receive Na-ASP-2 or hepatitis B vaccine. Major IgG and IgE epitopes of the Na-ASP-2 molecule were mapped by using sera from these same subjects. Seroepidemiologic studies in adults and children residing in hookworm-endemic areas were conducted to assess the prevalence of IgE responses to Na-ASP-2.


RESULTS
Vaccination with a single dose of Na-ASP-2 resulted in generalized urticarial reactions in several volunteers. These reactions were associated with pre-existing Na-ASP-2-specific IgE likely induced by previous hookworm infection. Surveys revealed that a significant proportion of the population in hookworm-endemic areas had increased levels of IgE to Na-ASP-2. Epitope mapping demonstrated sites on the Na-ASP-2 molecule that are uniquely or jointly recognized by IgG and IgE antibodies.


CONCLUSIONS
Infection with N americanus induces increased levels of total and specific IgE to Na-ASP-2 that result in generalized urticaria on vaccination with recombinant Na-ASP-2. These data advance knowledge of vaccine development for helminths given their propensity to induce strong T(H)2 responses. Study data highlight the important differences between the immune responses to natural helminth infection and to vaccination with a recombinant helminth antigen.
Albert B. Sabin Vaccine Institute, Washington, DC 20037, USA. david.diemert@sabin.org
David J
DJ
Diemert
Antonio G
AG
Pinto
Janaina
J
Freire
Amar
A
Jariwala
Helton
H
Santiago
Robert G
RG
Hamilton
Maria Victoria
MV
Periago
Alex
A
Loukas
Leon
L
Tribolet
Jason
J
Mulvenna
Rodrigo
R
Correa-Oliveira
Peter J
PJ
Hotez
Jeffrey M
JM
Bethony
D000293:Adolescent; D000328:Adult; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D018604:Epitope Mapping; D005260:Female; D015801:Helminth Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D017221:Necator americanus / Q000276:immunology*; D009332:Necatoriasis / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D016036:Seroepidemiologic Studies; D016896:Treatment Outcome; D014581:Urticaria / Q000453:epidemiology* / Q000209:etiology; D014611:Vaccination / Q000009:adverse effects; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D055815:Young Adult
D000947:Antigens, Helminth; D015801:Helminth Proteins; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E