title: Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant.
abstract: Previously, we have shown the potency of recombinant Adenovirus serotype 35 viral vaccines (rAd35) to induce strong immune response against the circumsporozoite protein (CS) of the plasmodium parasite. To further optimize immunogenicity of Ad35-based malaria vaccines we formulated rAd35.CS vaccine with aluminium phosphate adjuvant (AlPO(4)). In contrast to the conventional protein based vaccines no absorption to aluminium adjuvant was observed and rAd35 viral in vitro infectivity in mammalian cells was preserved. Immunization with Ad35.CS formulated with AlPO(4) resulted in significantly higher CS specific T and B cell responses in mice upon either single or prime-boost vaccination regimens as compared to rAd35.CS alone. With these results we report for the first time the feasibility of using an AlPO(4) adjuvant to increase the potency of a live adenovirus serotype 35-based vaccine.
authors.affiliation: Crucell Holland BV, P.O. Box 2048, 2301 CA Leiden, The Netherlands. o.ophorst@Crucell.com
authors.forename: Olga J A E
authors.initials: OJ
authors.lastname: Ophorst
authors.forename: Katarina
authors.initials: K
authors.lastname: Radosević
authors.forename: Jaco M
authors.initials: JM
authors.lastname: Klap
authors.forename: Jeroen
authors.initials: J
authors.lastname: Sijtsma
authors.forename: Gert
authors.initials: G
authors.lastname: Gillissen
authors.forename: Ratna
authors.initials: R
authors.lastname: Mintardjo
authors.forename: Mark J M
authors.initials: MJ
authors.lastname: van Ooij
authors.forename: Lennart
authors.initials: L
authors.lastname: Holterman
authors.forename: Arjen
authors.initials: A
authors.lastname: Companjen
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Menzo J E
authors.initials: MJ
authors.lastname: Havenga
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors; D007111:Immunity, Cellular / Q000276:immunology; D007117:Immunization, Secondary; D017780:Malaria Vaccines / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D017780:Malaria Vaccines; D010710:Phosphates; D014614:Vaccines, Synthetic; C012714:aluminum phosphate