Vaccination with a recombinant vaccinia vaccine containing the B7-1 co-stimulatory molecule causes no significant toxicity and enhances T cell-mediated cytotoxicity.
B7-1 is a co-stimulatory molecule that provides a second signal for T-cell activation. Several studies have demonstrated that vaccination with a vector containing genes encoding B7-1 and an antigen appears to be efficacious at promoting immune responsiveness to the antigen. To evaluate the safety of such a protocol and determine the effect of the B7-1 vector on immune responsiveness, female C57BL/6 mice were administered Wyeth wild-type vaccinia virus (V-WT) or V-WT containing the gene for B7-1 (rV-B7-1) as a single s. c. injection or 3 monthly s.c. injections. Immunologic parameters were evaluated in half of the mice and general toxicity in the other half. Immunologic end points included determination of splenic lymphocyte phenotypes, mitogen-induced T- and B-cell proliferation, T-cell proliferation in response to alloantigens, cell-mediated cytotoxicity (CMC), natural killer cell activity and serum anti-nuclear antibody (ANA) titers. No significant signs of general toxicity were noted. The primary immunologic effect was an increase in the ability of spleen cells to lyse allogeneic targets and to proliferate in response to allogeneic stimulation. Numbers of splenic CD8(+) cells were also increased. These effects were more pronounced after 3 vaccinations than after a single vaccination. Minimal differences in ANA were observed between mice immunized with V-WT and rV-B7-1. In addition, no serum antibodies against B7-1 were detected in any mice. The data suggest that vaccination with rV-B7-1 augments CMC with minimal toxicity.
Freund
Y R
YR
SRI International, Menlo Park, CA 94025-3493, USA. yvonne.freund@sri.com
Mirsalis
J C
JC
Fairchild
D G
DG
Brune
J
J
Hokama
L A
LA
Schindler-Horvat
J
J
Tomaszewski
J E
JE
Hodge
J W
JW
Schlom
J
J
Kantor
J A
JA
Tyson
C A
CA
Donohue
S J
SJ
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D001772:Blood Cell Count; D001806:Blood Urea Nitrogen; D003602:Cytotoxicity, Immunologic; D005260:Female; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000633:toxicity*; D014616:Vaccinia virus
D000974:Antibodies, Antinuclear; D018122:B7-1 Antigen; D014614:Vaccines, Synthetic; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase