title: Immunological responses against Plasmodium falciparum Apical Membrane Antigen 1 vaccines vary depending on the population immunized.
abstract: Clinical development of malaria vaccines progresses from trials in malaria naïve adults to malaria exposed adults followed by malaria exposed children. It is not well known whether immune responses in non-target populations are predictive of those in target populations, particularly in African children. Therefore humoral responses in three different populations (U.S. adults, Malian adults and Malian children) were compared in this study. They were immunized with 80 μg of Apical Membrane Antigen 1 (AMA1)/alhydrogel on days 0 and 28. Sera were collected on days 0 and 42; antibody levels were determined by ELISA and the functionality of antibodies was evaluated by Growth Inhibition Assay. After immunization, there was no significant difference in antibody levels between the Malian children and the Malian adults, but U.S. adults showed lower antibody levels. Vaccination did not significantly change growth-inhibitory activity in Malian adults, but inhibition increased significantly in both U.S. adults and Malian children. Vaccine-induced inhibitory activity was reversed by pre-incubation with AMA1 protein, but pre-existing infection-induced inhibition was not. This study shows that humoral responses elicited by the AMA1 vaccine varied depending on the population, most likely reflecting different levels of previous malaria exposure. Thus predicting immune responses from non-target populations is not desirable.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. kmiura@niaid.nih.gov
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Ababacar
authors.initials: A
authors.lastname: Diouf
authors.forename: Gregory
authors.initials: G
authors.lastname: Tullo
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Moretz
authors.forename: Joan A
authors.initials: JA
authors.lastname: Aebig
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Alassane
authors.initials: A
authors.lastname: Dicko
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Ruth D
authors.initials: RD
authors.lastname: Ellis
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D056724:Immunity, Humoral; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008302:Mali; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D014481:United States; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium