| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands
2 AERAS Global TB Vaccine Foundation, 7500 Old Georgetown Road, Bethesda, MD 20814, USA
3 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Correspondence
M. Havenga
m.havenga{at}crucell.com
Adenoviral vectors based on adenovirus type 35 (rAd35) have the advantage of low natural vector immunity and induce strong, insert-specific T- and B-cell responses, making them prime-candidate vaccine carriers. However, severe vector-genome instability of E1-deleted rAd35 vectors was observed, hampering universal use. The instability of E1-deleted rAd35 vector proved to be caused by low pIX expression induced by removal of the pIX promoter, which was located in the E1B region of B-group viruses. Reinsertion of a minimal pIX promoter resulted in stable vectors able to harbour large DNA inserts (>5 kb). In addition, it is shown that replacement of the E4-Orf6 region of Ad35 by the E4-Orf6 region of Ad5 resulted in successful propagation of an E1-deleted rAd35 vector on existing E1-complementing cell lines, such as PER.C6 cells. The ability to produce these carriers on PER.C6 contributes significantly to the scale of manufacturing of rAd35-based vaccines. Next, a stable rAd35 vaccine was generated carrying Mycobacterium tuberculosis antigens Ag85A, Ag85B and TB10.4. The antigens were fused directly, resulting in expression of a single polyprotein. This vaccine induced dose-dependent CD4+ and CD8+ T-cell responses against multiple antigens in mice. It is concluded that the described improvements to the rAd35 vector contribute significantly to the further development of rAd35 carriers for mass-vaccination programmes for diseases such as tuberculosis, AIDS and malaria.
Published online ahead of print on 2 May 2006 as DOI 10.1099/vir.0.81956-0.
This article has been cited by other articles:
|
|
 |
|
  R. Vogels, D. Zuijdgeest, M. van Meerendonk, A. Companjen, G. Gillissen, J. Sijtsma, I. Melis, L. Holterman, K. Radosevic, J. Goudsmit, et al. High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector J. Gen. Virol., November 1, 2007; 88(11): 2915 - 2924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Radosevic, C. W. Wieland, A. Rodriguez, G. J. Weverling, R. Mintardjo, G. Gillissen, R. Vogels, Y. A. W. Skeiky, D. M. Hone, J. C. Sadoff, et al. Protective Immune Responses to a Recombinant Adenovirus Type 35 Tuberculosis Vaccine in Two Mouse Strains: CD4 and CD8 T-Cell Epitope Mapping and Role of Gamma Interferon Infect. Immun., August 1, 2007; 75(8): 4105 - 4115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Abbink, A. A. C. Lemckert, B. A. Ewald, D. M. Lynch, M. Denholtz, S. Smits, L. Holterman, I. Damen, R. Vogels, A. R. Thorner, et al. Comparative Seroprevalence and Immunogenicity of Six Rare Serotype Recombinant Adenovirus Vaccine Vectors from Subgroups B and D J. Virol., May 1, 2007; 81(9): 4654 - 4663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. C. Lemckert, J. Grimbergen, S. Smits, E. Hartkoorn, L. Holterman, B. Berkhout, D. H. Barouch, R. Vogels, P. Quax, J. Goudsmit, et al. Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: manufacture on PER.C6 cells, tropism and immunogenicity. J. Gen. Virol., October 1, 2006; 87(Pt 10): 2891 - 2899. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
