Oral immunization with enterocoated microbeads induces antigen-specific cytolytic T-cell responses.
A cytolytic T-lymphocyte (CTL) response has been generated to a protein antigen via oral administration in an experimental murine system. This was achieved by the formulation of the test antigen ovalbumin (OVA) in a pH-sensitive microsphere particle (microbead) with an acrylic-based coating to avoid its degradation by gastric enzymes. Comparative studies of orally administered enterocoated microbead-OVA particles, versus the more traditional formulation of OVA in adjuvant (DETOX-PC) given subcutaneously as immunogen, were conducted; both elicited comparable responses in the generation of antigen-specific lymphoproliferative and CTL responses. CTL lines generated via oral administration of antigen were shown to be CD3(+), CD4(-), and CD8(+). CTL lysis of OVA peptide-pulsed targets was shown to be inhibited by anti-CD8 antibody. Whereas oral administration of pH-sensitive enterocoated microbeads containing proteins has previously been shown to elicit antibody and lymphoproliferative T-cell responses to protein antigens, this is the first demonstration of the generation of an antigen-specific cytolytic T-cell response via oral administration of a protein immunogen formulated in such microbeads.
Vogel
K
K
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Kantor
J
J
Wood
L
L
Rivera
R
R
Schlom
J
J
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000941:Antigens / Q000008:administration & dosage*; D002460:Cell Line; D002645:Chickens; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D010446:Peptide Fragments; D010047:Ovalbumin