title: Antigen capsid-display on human adenovirus 35 via pIX fusion is a potent vaccine platform.
abstract: Durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. While heterologous prime-boost regimens based on recombinant, replication-incompetent Adenoviral vectors (AdV) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. To combine the benefits of genetic and protein-based vaccination within one vaccine construct and to facilitate their use, we generated Human Adenovirus 35 (HAdV35) vectors genetically encoding a model antigen based on the Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein and displaying a truncated version of the same antigen (CSshort) via protein IX on the capsid, with or without a flexible glycine-linker and/or a 45Å-spacer. The four tested pIX-antigen display variants were efficiently incorporated and presented on the HAdV35 capsid irrespective of whether a transgene was encoded or not. Transgene-expression and producibility of the display-/expression vectors were not impeded by the pIX-display. In mice, the pIX-modified vectors induced strong humoral antigen-specific immunity that increased with the inclusion of the linker-/spacer molecules, exceeded the responses induced by the genetic, transgene-expressing HAdV35 vector, and surpassed recombinant protein in potency. In addition, the pIX- display/expression vectors elicited high antigen-specific cellular immune responses that matched those of the genetic HAdV35 vector expressing CS. pIX-modified display-/expression HAdV vectors may therefore be a valuable technology for the development of vaccines against complex pathogens, especially in resource-limited settings.
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Nadine C
authors.initials: NC
authors.lastname: Salisch
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Marija
authors.identifier: http://orcid.org/0000-0001-7167-7041
authors.initials: M
authors.lastname: Vujadinovic
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: van der Helm
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Spek
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Lars
authors.initials: L
authors.lastname: Vorthoren
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Serroyen
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Harmjan
authors.initials: H
authors.lastname: Kuipers
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Roland
authors.initials: R
authors.lastname: Zahn
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Jerome
authors.initials: J
authors.lastname: Custers
authors.affiliation: Janssen Vaccines & Prevention, Leiden, The Netherlands.
authors.forename: Jort
authors.initials: J
authors.lastname: Vellinga
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors / Q000235:genetics*; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D010963:Plasmodium falciparum / Q000276:immunology*
chemical_list: D036022:Capsid Proteins; D017780:Malaria Vaccines