title: Vaccination of monkeys with recombinant Plasmodium falciparum apical membrane antigen 1 confers protection against blood-stage malaria.
abstract: A major challenge facing malaria vaccine development programs is identifying efficacious combinations of antigens. To date, merozoite surface protein 1 (MSP1) is regarded as the leading asexual vaccine candidate. Apical membrane antigen 1 (AMA1) has been identified as another leading candidate for an asexual malaria vaccine, but without any direct in vivo evidence that a recombinant form of Plasmodium falciparum AMA1 would have efficacy. We evaluated the efficacy of a form of P. falciparum AMA1, produced in Pichia pastoris, by vaccinating Aotus vociferans monkeys and then challenging them with P. falciparum parasites. Significant protection from this otherwise lethal challenge with P. falciparum was observed. Five of six animals had delayed patency; two of these remained subpatent for the course of the infection, and two controlled parasite growth at <0.75% of red blood cells parasitized. The protection induced by AMA1 was superior to that obtained with a form of MSP1 used in the same trial. The protection induced by a combination vaccine of AMA1 and MSP1 was not superior to the protection obtained with AMA1 alone, although the immunity generated appeared to operate against both vaccine components.
authors.affiliation: Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA. anthony_stowers@csl.com.au
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Stowers
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kennedy
authors.forename: Brian P
authors.initials: BP
authors.lastname: Keegan
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Louis H
authors.initials: LH
authors.lastname: Miller
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan; D016645:Aotidae; D004912:Erythrocytes / Q000469:parasitology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology; D018512:Parasitemia / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic; C090077:apical membrane antigen I, Plasmodium