Keyhole limpet haemocyanin - a model antigen for human immunotoxicological studies

被引:73
作者
Swaminathan, Ashwin [1 ,2 ,3 ]
Lucas, Robyn M. [1 ,4 ]
Dear, Keith [5 ]
McMichael, Anthony J. [1 ]
机构
[1] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT 0200, Australia
[2] Canberra Hosp, Infect Dis Unit, Canberra, ACT, Australia
[3] Canberra Hosp, Gen Med Unit, Canberra, ACT, Australia
[4] Univ Western Australia, Telethon Kids Inst, Perth, WA 6009, Australia
[5] Duke Kunshan Univ, Duke Global Hlth Inst, Kunshan, Jiangsu, Peoples R China
基金
英国医学研究理事会;
关键词
clinical studies; immunization; immunotoxicology; keyhole limpet haemocyanin; KLH; PRIMARY IMMUNE-RESPONSE; PRIMARY ANTIBODY-RESPONSE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HEALTHY-VOLUNTEERS; BLADDER-CANCER; OLDER-ADULTS; IN-VIVO; KLH; IMMUNIZATION; VACCINES;
D O I
10.1111/bcp.12422
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Immunization with a T-cell dependent antigen has been promoted as a reliable and sensitive tool for assessing the influence of putative immunotoxic exposures or agents on immune function. Keyhole limpet haemocyanin (KLH) is a very large, copper-containing protein molecule derived from the haemolymph of the inedible mollusc, Megathura crenulata. KLH is a highly immunogenic T-cell dependent antigen that is used increasingly in immunotoxicological studies, particularly in those involving animals. This report systematically reviews the human clinical studies that have used trans-cutaneous KLH immunization for assessment of the influence of various physiological and disease states and exposures on immune function over the last 20 years (1994-2013). These studies varied in their immunization protocols, formulation of KLH, dose, site and route of administration and immunoassay platforms developed to assess KLH-specific responses. KLH immunization has been well tolerated with only mild to moderate adverse effects reported. Though very promising as a model antigen candidate in immunotoxicology research, more work on standardizing immunization and immunoassay protocols is required.
引用
收藏
页码:1135 / 1142
页数:8
相关论文
共 51 条
[1]  
AMLOT PL, 1986, CLIN EXP IMMUNOL, V64, P125
[2]   The use of oil adjuvants in therapeutic vaccines [J].
Aucouturier, J ;
Ascarateil, S ;
Dupuis, L .
VACCINE, 2006, 24 :S44-S45
[3]   Immunization Responses in Rheumatoid Arthritis Patients Treated With Rituximab Results From a Controlled Clinical Trial [J].
Bingham, Clifton O., III ;
Looney, R. John ;
Deodhar, Atul ;
Halsey, Neal ;
Greenwald, Maria ;
Codding, Christine ;
Trzaskoma, Benjamin ;
Martin, Flavius ;
Agarwal, Sunil ;
Kelman, Ariella .
ARTHRITIS AND RHEUMATISM, 2010, 62 (01) :64-74
[4]  
Biosyn Corporation, VACM IMM PROD INF
[5]   Primary immune response to keyhole limpet haemocyanin following trauma in relation to low plasma glutamine [J].
Boelens, PG ;
Fonk, JCM ;
Houdijk, APJ ;
Scheper, RJ ;
Haarman, HJTM ;
Meijer, S ;
Van Leeuwen, PAM ;
Von Blomberg-Van Der Flier, BME .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2004, 136 (02) :356-364
[6]   Pharmacodynamic Effects of Steady-State Fingolimod on Antibody Response in Healthy Volunteers: A 4-Week, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Dose Study [J].
Boulton, Craig ;
Meiser, Karin ;
David, Olivier J. ;
Schmouder, Robert .
JOURNAL OF CLINICAL PHARMACOLOGY, 2012, 52 (12) :1879-1890
[7]   T-Dependent antigen response (TDAR) tests: Meta-analysis of results generated across multiple laboratories [J].
Bugelski, Peter J. ;
Kim, Carin .
JOURNAL OF IMMUNOTOXICOLOGY, 2007, 4 (02) :159-164
[8]   Breast cancer vaccines: a clinical reality or fairy tale? [J].
Curigliano, G ;
Spitaleri, G ;
Pietri, E ;
Rescigno, M ;
de Braud, F ;
Cardillo, A ;
Munzone, E ;
Rocca, A ;
Bonizzi, G ;
Brichard, V ;
Orlando, L ;
Goldhirsch, A .
ANNALS OF ONCOLOGY, 2006, 17 (05) :750-762
[9]  
CURTIS JE, 1970, CLIN EXP IMMUNOL, V6, P473
[10]   A novel assay to measure B cell responses to keyhole limpet haemocyanin vaccination in healthy volunteers and subjects with systemic lupus erythematosus [J].
Ferbas, John ;
Belouski, Shelley S. ;
Horner, Michelle ;
Kaliyaperumal, Arunan ;
Chen, Li ;
Boyce, Malcolm ;
Colaco, C. Bernie ;
McHugh, Neil ;
Quick, Vanessa ;
Nicholl, Richard J. ;
Siu, Gerald ;
Chung, James .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 76 (02) :188-202