title: Adenovectors induce functional antibodies capable of potent inhibition of blood stage malaria parasite growth.
abstract: An effective malaria vaccine remains a global health priority. Recombinant adenoviruses are a promising vaccine platform, and Plasmodium falciparum apical membrane antigen 1 (AMA1) and merozoite surface protein 1-42 (MSP1(42)) are leading blood stage vaccine candidates. We evaluated the importance of surface antigen localization and glycosylation on the immunogenicity of adenovector delivered AMA1 and MSP1(42) and assessed the ability of these vaccines to induce functional antibody responses capable of inhibiting parasite growth in vitro. Adenovector delivery induced unprecedented levels of biologically active antibodies in rabbits as indicated by the parasite growth inhibition assay. These responses were as potent as published results using any other vaccine system, including recombinant protein in adjuvant. The cell surface associated and glycosylated forms of AMA1 and MSP1(42) elicited 99% and 60% inhibition of parasite growth, respectively. Antigens that were expressed at the cell surface and glycosylated were much better than intracellular antigens at inducing antibody responses. Good T cell responses were observed for all forms of AMA1 and MSP1(42). Antigen-specific antibody responses, but typically not T cell responses, were boosted by a second administration of adenovector. These data highlight the importance of rational vaccine design and support the advancement of adenovector delivery technology for a malaria vaccine.
authors.affiliation: GenVec, Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20878, USA. jbruder@genvec.com
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Bruder
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Stefaniak
authors.forename: Noelle B
authors.initials: NB
authors.lastname: Patterson
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Svetlana
authors.initials: S
authors.lastname: Konovalova
authors.forename: Keith
authors.initials: K
authors.lastname: Limbach
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Campo
authors.forename: Damodar
authors.initials: D
authors.lastname: Ettyreddy
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Filip
authors.initials: F
authors.lastname: Dubovsky
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: C Richter
authors.initials: CR
authors.lastname: King
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D006031:Glycosylation; D007117:Immunization, Secondary / Q000379:methods; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium