title: Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques.
abstract: A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a multicomponent, multistage DNA vaccine for the simian malaria species Plasmodium knowlesi including two preerythrocytic-stage antigens, the circumsporozoite protein (PkCSP) and sporozoite surface protein 2 (PkSSP2), and two blood stage antigens, apical merozoite antigen 1 (PkAMA1) and merozoite surface protein 1 (PkMSP1p42), as well as recombinant canarypox viruses encoding the four antigens (ALVAC-4). The DNA vaccine plasmids expressed the corresponding antigens in vitro and induced antiparasite antibodies in mice. Groups of four rhesus monkeys received three doses of a mixture of the four DNA vaccine plasmids and a plasmid encoding rhesus granulocyte-monocyte colony-stimulating factor, followed by boosting with a single dose of ALVAC-4. Three groups received the priming DNA doses by different routes, either by intramuscular needle injection, by intramuscular injection with a needleless injection device, the Biojector, or by a combination of intramuscular and intradermal routes by Biojector. Animals immunized by any route developed antibody responses against sporozoites and infected erythrocytes and against a recombinant PkCSP protein, as well as gamma interferon-secreting T-cell responses against peptides from PkCSP. Following challenge with 100 P. knowlesi sporozoites, 1 of 12 experimental monkeys was completely protected and the mean parasitemia in the remaining monkeys was significantly lower than that in 4 control monkeys. This model will be important in preclinical vaccine development.
authors.affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910, Bethesda, Maryland 20889, USA. Rogersb@nmrc.navy.mil
authors.forename: W O
authors.initials: WO
authors.lastname: Rogers
authors.forename: J K
authors.initials: JK
authors.lastname: Baird
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: J A
authors.initials: JA
authors.lastname: Tine
authors.forename: W
authors.initials: W
authors.lastname: Weiss
authors.forename: J C
authors.initials: JC
authors.lastname: Aguiar
authors.forename: K
authors.initials: K
authors.lastname: Gowda
authors.forename: R
authors.initials: R
authors.lastname: Gwadz
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: M
authors.initials: M
authors.lastname: Gold
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018150:Avipoxvirus / Q000235:genetics* / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D008253:Macaca mulatta; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D018512:Parasitemia / Q000517:prevention & control; D010957:Plasmids / Q000235:genetics; D016790:Plasmodium knowlesi / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma