Abstract/Details

Designing and testing the efficacy of recombinant idiotype -mycobacterial HSP70 fusion protein as a vaccine model against B -cell lymphomas


2007 2007

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Abstract (summary)

Objectives. Variable regions of immunoglobulin molecule (Ig) on B-cell lymphoma constitute tumor specific antigenic determinants collectively designated as idiotype (Id). Idiotypic determinants are nominally antigenic in tumor bearing hosts. Mycobacterial heat shock protein 70 (mycHSP70) is known for its ability as immunoadjuvant to activate anigen-presenting cells such as dendritic cells (DCs) through a toll-like receptor, TLR4. The objective of this study is to utilize mycHSP70 to enhance immunogenicity of two different B-lymphoma specific idiotopes. We accomplished this by using mycHSP70 fused to idiotypes of two tumors A20 and 2C3 as recombinant protein vaccine. Methods. By using standard molecular techniques we constructed plasmids encoding idiotype-mycHSP70 recombinant proteins (A20Id-mycHSP70, 2C3Id-mycHSP70). Purified recombinant proteins were tested for their efficacy as vaccines. Results. Our study showed that A20Id-mycHSP70 as vaccine elicited significantly higher anti-idiotype humoral responses which were predominantly IgG2a type. This suggests activation/involvement of T-helper type 1 cells. Tumor-challenged mice also experienced long-term protection (mean survival rate 40% higher than control groups) with prophylactic vaccination using A20Id-mycHSP70 protein. Concomitant with this increased survival rate, there was a significant increase in idiotype-specific cytotoxic T-cell responses. In contrast, no significant differences were observed between 2C3Id-mycHSP70 and control groups in terms of humoral and cellular immune responses as well as by survival studies. Conclusion. Immunogenicity of A20 idiotype but not 20 idiotype can be significantly enhanced by its covalent coupling with mycobacterial HSP70. The differences can be explained on the basis of presence or absence of MHC class I binding epitopes in 2C3 idiotype but not in A20 idiotype. However, both the idiotypes were found to have potential MHC II epitopes. In essence, this study suggests that mycHSP70 can be used as an adjuvant to enhance Id immunogenicity provided, the antigen has appropriate MHC epitopes.

Indexing (details)


Subject
Microbiology;
Immunology
Classification
0410: Microbiology
0982: Immunology
Identifier / keyword
Health and environmental sciences; Biological sciences; B cell lymphomas; Fusion proteins; Heat shock proteins; Idiotype; Immunology; Mycobacterial HSP70; Vaccines
Title
Designing and testing the efficacy of recombinant idiotype -mycobacterial HSP70 fusion protein as a vaccine model against B -cell lymphomas
Author
Karyampudi, Lavakumar
Number of pages
124
Publication year
2007
Degree date
2007
School code
0094
Source
DAI-B 68/10, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549285977
Advisor
Ghosh, Swapan
University/institution
Indiana State University
University location
United States -- Indiana
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3286434
ProQuest document ID
304859353
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304859353
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