scholarly journals A highly specific antibody response after protein prime-peptide boost immunization with Eppin/B-cell epitope in mice

2011 ◽  
Vol 7 (8) ◽  
pp. 849-855 ◽  
Author(s):  
Zhengqiong Chen ◽  
Wei He ◽  
Yuzhang Wu ◽  
Ping Yan ◽  
Haiyang He ◽  
...  
Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 343-354 ◽  
Author(s):  
Tian-Ying Zhang ◽  
Xue-Ran Guo ◽  
Yang-Tao Wu ◽  
Xiao-Zhen Kang ◽  
Qing-Bing Zheng ◽  
...  

ObjectiveThis study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models.MethodsA series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically.ResultsAmong the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance.ConclusionsThe novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.


Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 704-710 ◽  
Author(s):  
Ernest T. Parker ◽  
John F. Healey ◽  
Rachel T. Barrow ◽  
Heather N. Craddock ◽  
Pete Lollar

AbstractApproximately 25% of patients with hemophilia A develop inhibitory antibodies after treatment with factor VIII. Most of the inhibitory activity is directed against epitopes in the A2 and C2 domains. Anti-A2 inhibitory antibodies recognize a 25-residue segment bounded by R484-I508. Several antigenic residues in this segment have been identified, including R484, R489, and P492. The immunogenicity of purified recombinant B domain–deleted (BDD) human factor VIII molecules containing mutations at R484A/R489A or R484A/R489A/P492A was studied in hemophilia A mice. Inhibitory antibody titers in mice receiving the R484A/R489A/P492A mutant, but not the R484A/R489A mutant, were significantly lower than in mice receiving control human BDD factor VIII. The specific coagulant activity and the in vivo clearance and hemostatic efficacy in hemophilia A mice of the R484A/R489A/P492A mutant were indistinguishable from human BDD factor VIII. Thus, the inhibitory antibody response to human factor VIII can be reduced by mutagenesis of a B-cell epitope without apparent loss of function, suggesting that this approach may be useful for developing a safer form of factor VIII in patients with hemophilia A.


2012 ◽  
Vol 56 (04) ◽  
pp. 337-342 ◽  
Author(s):  
KEE-BUM PARK ◽  
BYUNG-KWAN LIM ◽  
MICHAEL B. YE ◽  
SOO-YOUNG CHUNG ◽  
JAE-HWAN NAM

Author(s):  
Pravin TP Kaumaya

In light of the numerous US FDA-approved humanized monoclonal antibodies (mAbs) for cancer immunotherapy, it is surprising that the advancement of B-cell epitope vaccines designed to elicit a natural humoral polyclonal antibody response has not gained traction in the immune-oncology landscape. Passive immunotherapy with humanized mAbs (Trastuzumab [Herceptin®]; Pertuzumab [Perjeta®]) has provided clinical benefit to breast cancer patients, albeit with significant shortcomings including toxicity problems and resistance, high costs, sophisticated therapeutic regimen and long half-life. The role of B-cell humoral immunity in cancer is under appreciated and underdeveloped. We have advanced the idea of active immunotherapy with chimeric B-cell epitope peptides incorporating a ‘promiscuous’ T-cell epitope that elicits a polyclonal antibody response, which provides safe, cost–effective therapeutic advantage over mAbs. We have created a portfolio of validated B-cell peptide epitopes against multiple receptor tyrosine kinases (HER-1, HER-3, IGF-1R and VEGF). We have successfully translated two HER-2 combination B-cell peptide vaccines in Phase I and II clinical trials. We have recently developed an effective novel programmed cell death-1 vaccine. In this article, I will review our approaches and strategies that focus on B-cell epitope cancer vaccines.


PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0172524 ◽  
Author(s):  
Juan Pablo Jaworski ◽  
Peter Bryk ◽  
Zachary Brower ◽  
Bo Zheng ◽  
Ann J. Hessell ◽  
...  

2018 ◽  
Vol 65 (2) ◽  
pp. e457-e469 ◽  
Author(s):  
K. De Puysseleyr ◽  
E. Kieckens ◽  
L. De Puysseleyr ◽  
H. Van den Wyngaert ◽  
B. Ahmed ◽  
...  

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