Characterization of antigen-specific immune responses induced by canarypox virus vaccines.
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.
Bos
Rinke
R
Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Leiden University Medical Center, Leiden, The Netherlands.
van Duikeren
Suzanne
S
van Hall
Thorbald
T
Lauwen
Marjolein M
MM
Parrington
Mark
M
Berinstein
Neil L
NL
McNeil
Bryan
B
Melief
Cornelis J M
CJ
Verbeek
J Sjef
JS
van der Burg
Sjoerd H
SH
Offringa
Rienk
R
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D028121:Canarypox virus / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D012680:Sensitivity and Specificity; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000956:Antigens, Viral; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D000939:Epitopes; D014765:Viral Vaccines