Local immune responses to influenza antigen are synergistically enhanced by the adjuvant ISCOMATRIX

• Published in: Vaccine Vol. 20; no. 3; pp. 490 - 497
• Main Authors: Windon, R.G., Chaplin, P.J., McWaters, P., Tavarnesi, M., Tzatzaris, M., Kimpton, W.G., Cahill, R.N.P., Beezum, L., Coulter, A., Drane, D., Sjölander, A., Pearse, M., Scheerlinck, J-P.Y., Tennent, J.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 12.11.2001; Elsevier
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Viral - blood; Antigens, Viral - immunology; Applied microbiology; Biological and medical sciences; Cytokines - biosynthesis; Epidemiology. Vaccinations; Fundamental and applied biological sciences. Psychology; General aspects; Infectious diseases; Influenza antigen; Interleukin-6 - biosynthesis; ISCOMATRIX; ISCOMs - pharmacology; Lymphatic duct cannulation; Lymphocyte Activation; Medical sciences; Microbiology; Orthomyxoviridae - immunology; Sheep; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); IL-1β, interleukin 1β; IL-2, interleukin 2; TMB, tetramethyl benzidine; IL-6, interleukin 6; Flu ag, human influenza virus antigen; IFN-γ, interferon gamma; HRP, horseradish peroxidase; Con A, concanavalin A; IMX, ISCOMATRIX; Influenza antigen; APCs, antigen presenting cells; RT, room temperature; TNFα, tumour necrosis factor alpha; GM-CSF, granulocyte macrophage colony stimulating factor; ISCOMs ®, immune stimulating complexes; 3H-T, 3H-thymidine; PBS, phosphate buffered saline; ISCOMATRIX; Lymphatic duct cannulation; EIA, enzyme immunoassay; HA, haemagglutinin; PBST, PBS containing 0.05% Tween 20; S.E.M., standard error of mean; DMEM, Dulbecco’s modified Eagle’s medium; Total Ig, total immunoglobulin; IL-8, interleukin 8; LPS, lipopolysaccharide; Infection; Antigen; Immune response; Viral disease; Influenza
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(01)00332-2

The peripheral (draining) lymph node, as the primary site of immune induction, determines the course of systemic responses to an injected antigen. Lymphatic duct cannulation procedures in sheep were used to investigate local immunoreactivity to human influenza virus antigen (Flu ag) admixed with the adjuvant ISCOMATRIX ® (IMX). Compared to Flu ag or IMX alone, the co-administration of Flu ag and IMX (Flu ag+IMX) synergistically enhanced a number of immunological responses (lymphocyte and blast migration from the node, antigen-specific antibody levels and IL6 output in efferent lymph, and antigen-induced proliferation in cultured efferent lymph cells). Together, these results demonstrate that IMX is an immune modulator, and that lymphatic duct cannulation procedures may be used to evaluate antigen/adjuvant combinations for vaccine development.