Document Detail

A vaccine conjugate of 'ISCAR' immunocarrier and peptide epitopes of the E7 cervical cancer-associated protein of human papillomavirus type 16 elicits specific Th1- and Th2-type responses in immunized mice in the absence of oil-based adjuvants.
MedLine Citation:
PMID:  7544248     Owner:  NLM     Status:  MEDLINE    
TraT protein, known as ISCAR (= Immunostimulatory Carrier), is one of a family of integral membrane proteins (Imps) of Escherichia coli representing powerful carrier molecules which when injected into experimental animals generate substantial antibody and T proliferative responses to molecules conjugated to it. We extend these findings to show that ISCAR functions to stimulate Th1- and Th2-type responses, including specific cytotoxic T cells and tumour protection. We report here that by conjugating to ISCAR a 19mer peptide containing linear B epitopes, a T helper (Th) epitope, and a H-2b-restricted T cytotoxic (CTL) epitope of E7 protein of human papillomavirus type 16 (HPV16), and immunizing C57B1/6 (H-2b) mice, we elicited (i) specific IgG2a and IgG1 antibodies; (ii) IL-2 and IL-4 production by specifically recalled lymph node cells in vitro; (iii) cytotoxic T lymphocytes which specifically killed both E7 peptide-pulsed, and whole E7 gene-transfected tumour target cells; and (iv) in vivo protection against an E7 gene-transfected tumour cell inoculum. These findings have implications for the design of vaccines to stimulate immune responses to endogenously processed target antigens (e.g. tumour-associated antigens) without the unwanted side effects of oil-based adjuvants. In addition they support the case for a E7-targeted therapeutic vaccine for HPV-associated human cervical cancer.
R W Tindle; S Croft; K Herd; K Malcolm; A F Geczy; T Stewart; G J Fernando
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  101     ISSN:  0009-9104     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-09-22     Completed Date:  1995-09-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  265-71     Citation Subset:  IM; X    
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
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MeSH Terms
Adjuvants, Immunologic / pharmacology*
Amino Acid Sequence
Antibodies, Viral / biosynthesis,  blood
Antigens, Neoplasm / immunology
Bacterial Outer Membrane Proteins / immunology*
Epitopes / immunology*
Escherichia coli Proteins*
Interleukin-2 / biosynthesis
Interleukin-4 / biosynthesis
Lymphocyte Activation / drug effects,  immunology
Mice, Inbred C57BL
Molecular Sequence Data
Neoplasms, Experimental / prevention & control
Oncogene Proteins, Viral / immunology*
Papillomavirus Vaccines*
T-Lymphocytes, Cytotoxic / immunology,  metabolism
Th1 Cells / drug effects,  immunology*,  metabolism
Th2 Cells / drug effects,  immunology*,  metabolism
Vaccines, Conjugate / pharmacology
Viral Vaccines / pharmacology*
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antibodies, Viral; 0/Antigens, Neoplasm; 0/Bacterial Outer Membrane Proteins; 0/Epitopes; 0/Escherichia coli Proteins; 0/Interleukin-2; 0/Oncogene Proteins, Viral; 0/Papillomavirus Vaccines; 0/TraT protein, E coli; 0/Vaccines, Conjugate; 0/Viral Vaccines; 0/oncogene protein E7, Human papillomavirus type 16; 207137-56-2/Interleukin-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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