| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunohematology and Blood Transfusion, Tumor Immunology Group,
Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands; and
Sanofi Pasteur, Toronto, Ontario, Canada
Avipoxvirus-based vectors, such as recombinant canarypox virus ALVAC, are studied extensively as delivery vehicles for vaccines against cancer and infectious diseases. Effective use of such vaccines is expected to benefit from proper understanding of the interaction between these viral vectors and the host immune system. We performed preclinical vaccination experiments in a murine tumor model to analyze the immunogenic properties of an ALVAC-based vaccine against carcinoembryonic Ag (ALVAC-CEA), a tumor-associated autoantigen commonly overexpressed in colorectal cancers. The protective CEA-specific immunity induced by this vaccine consisted of CD4+ T cell responses with a mixed Th1/Th2 cytokine profile that were accompanied by potent humoral responses, but not by CEA-specific CD8+ CTL immunity. In contrast, protective immunity induced by a CEA-specific DNA vaccine (DNA-CEA) consisted of Th1 and CTL responses. Modification of the ALVAC-CEA vaccine through coinjection of DNA-CEA, admixture with CpG oligodeoxynucleotides, or supplementation with additional transgenes encoding a triad of costimulatory molecules (TRICOM) did not result in induction of CEA-specific CTL responses. Even though these results suggested that ALVAC does not elicit Ag-specific CTLs, immunization with ALVAC vaccines against other Ags efficiently induced CTL responses. Our data show that the capacity of ALVAC vaccines to elicit CTL immunity against transgene-encoded Ags critically depends on the presence of highly immunogenic CTL epitopes in these Ags. This consideration needs to be taken into account with respect to the design and evaluation of vaccination strategies that use ALVAC-based vaccine.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Sanofi Pasteur Toronto and by Grant UL 2000-2035 from the Dutch Cancer Society.
2 Address correspondence and reprint requests to Dr. Rienk Offringa, Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, E3-Q, Leiden University Medical Center, Albinusdreef 2, 2333 RA Leiden, The Netherlands. E-mail address: R.Offringa{at}LUMC.nl
3 Abbreviations used in this paper: CEA, carcinoembryonic Ag; HPV, human papillomavirus; ADCC, Ab-dependent cellular cytotoxicity; ODN, oligodeoxynucleotide.
This article has been cited by other articles:
|
|
 |
|
  S. Kim-Schulze, H. S. Kim, A. Wainstein, D. W. Kim, W. C. Yang, D. Moroziewicz, P. Y. Mong, M. Bereta, B. Taback, Q. Wang, et al. Intrarectal Vaccination with Recombinant Vaccinia Virus Expressing Carcinoembronic Antigen Induces Mucosal and Systemic Immunity and Prevents Progression of Colorectal Cancer J. Immunol., December 1, 2008; 181(11): 8112 - 8119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bos, S. van Duikeren, H. Morreau, K. Franken, T. N.M. Schumacher, J. B. Haanen, S. H. van der Burg, C. J.M. Melief, and R. Offringa Balancing between Antitumor Efficacy and Autoimmune Pathology in T-Cell-Mediated Targeting of Carcinoembryonic Antigen Cancer Res., October 15, 2008; 68(20): 8446 - 8455. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
