title: Impact of recombinant adenovirus serotype 35 priming versus boosting of a Plasmodium falciparum protein: characterization of T- and B-cell responses to liver-stage antigen 1.
abstract: Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite (CS) protein improved significantly when the protein is primed with recombinant adenovirus serotype 35 coding for CS (rAd35.CS). The current study was designed to answer the question whether such an effect can be extended to liver-stage antigens (LSA) of Plasmodium falciparum such as LSA-1. Studies with mice have demonstrated that the LSA-1 protein induces strong antibody response but a weak T-cell immunity. We first identified T-cell epitopes in LSA-1 by use of intracellular gamma interferon (IFN-gamma) staining and confirmed these epitopes by means of enzyme-linked immunospot assay and pentamer staining. We show that a single immunization with rAd35.LSA-1 induced a strong antigen-specific IFN-gamma CD8(+) T-cell response but no measurable antibody response. In contrast, vaccinations with the adjuvanted recombinant LSA-1 protein induced remarkably low cellular responses but strong antibody responses. Finally, both priming and boosting of the adjuvanted protein by rAd35 resulted in enhanced T-cell responses without impairing the level of antibody responses induced by the protein immunizations alone. Furthermore, the incorporation of rAd35 in the vaccination schedule led to a skewing of LSA-1-specific antibody responses toward a Th1-type immune response. Our results show the ability of rAd35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule without impairing the B-cell response.
authors.affiliation: Crucell Holland BV, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands. Katarina.Radosevic@crucell.com
authors.forename: Ariane
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Arjen
authors.initials: A
authors.lastname: Companjen
authors.forename: Ratna
authors.initials: R
authors.lastname: Mintardjo
authors.forename: Gert
authors.initials: G
authors.lastname: Gillissen
authors.forename: Dennis
authors.initials: D
authors.lastname: Tax
authors.forename: Jeroen
authors.initials: J
authors.lastname: Sijtsma
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Lennart
authors.initials: L
authors.lastname: Holterman
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
authors.forename: Menzo J E
authors.initials: MJ
authors.lastname: Havenga
authors.forename: Katarina
authors.initials: K
authors.lastname: Radosevic
mesh_terms: D000256:Adenoviridae; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D005260:Female; D007117:Immunization, Secondary; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic