Carrier protein conjugate vaccines: the "missing link" to improved antibody and CTL responses?
There's still plenty "missing" from attempts to immunize against cancer and other pesky pathogens. Conjugation of weakly-immunogenic tumor-derived proteins or other pathogen-associated antigens to highly-immunogenic carrier proteins has long been utilized as a tool for improving immune responses. Such vaccines have recently been tested in phase 3 clinical trials targeting non-Hodgkin's B cell lymphoma. However, these vaccines, composed of tumor-specific immunoglobulin ("idiotype") protein linked to keyhole limpet hemocyanin using glutaraldehyde, largely failed to show efficacy. Yet substituting a sulfhydryl-based linker cleavable in lysosomes markedly augments the efficacy of these vaccines, offering heightened antibody and CTL responses. Could such conjugation strategies be the "missing link" needed in vaccines against pathogens requiring both antibodies and T cells for protection?
Timmerman
John M
JM
Division of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1678, USA. jtimmerman@mednet.ucla.edu
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006433:Hemocyanins / Q000494:pharmacology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic; D014612:Vaccines / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000941:Antigens; D002352:Carrier Proteins; D014612:Vaccines; D018074:Vaccines, Conjugate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin