title: Vaccination with an adenoviral vector that encodes and displays a retroviral antigen induces improved neutralizing antibody and CD4+ T-cell responses and confers enhanced protection.
abstract: We present a new type of adenoviral vector that both encodes and displays a vaccine antigen on the capsid, thus combining in itself gene-based and protein vaccination; this vector resulted in an improved vaccination outcome in the Friend virus (FV) model. For presentation of the envelope protein gp70 of Friend murine leukemia virus on the adenoviral capsid, gp70 was fused to the adenovirus capsid protein IX. When compared to vaccination with conventional FV Env- and Gag-encoding adenoviral vectors, vaccination with the adenoviral vector that encodes and displays pIX-gp70 combined with an FV Gag-encoding vector resulted in significantly improved protection against systemic FV challenge infection, with highly controlled viral loads in plasma and spleen. This improved protection correlated with improved neutralizing antibody titers and stronger CD4(+) T-cell responses. Using a vector that displays gp70 without encoding it, we found that while the antigen display on the capsid alone was sufficient to induce high levels of binding antibodies, in vivo expression was necessary for the induction of neutralizing antibodies. This new type of adenovirus-based vaccine could be a valuable tool for vaccination.
authors.affiliation: Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Universitaetsstr. 150, Bldg. MA, Rm. 6-40, D-44801 Bochum, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Bayer
authors.forename: Matthias
authors.initials: M
authors.lastname: Tenbusch
authors.forename: Ruth
authors.initials: R
authors.lastname: Lietz
authors.forename: Lena
authors.initials: L
authors.lastname: Johrden
authors.forename: Simone
authors.initials: S
authors.lastname: Schimmer
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Wildner
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D005622:Friend murine leukemia virus / Q000235:genetics* / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D007942:Leukemia, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012192:Retroviridae Infections / Q000276:immunology / Q000517:prevention & control; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D014759:Viral Envelope Proteins; D014765:Viral Vaccines