A peptide vaccine based on a B-cell epitope on the VP1 protein of enterovirus 70 induces a strong antibody response

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.


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.


2014 ◽  
Vol 192 (12) ◽  
pp. 5813-5820 ◽  
Author(s):  
Esther D. Quakkelaar ◽  
Marieke F. Fransen ◽  
Wendy W. C. van Maren ◽  
Joost Vaneman ◽  
Nikki M. Loof ◽  
...  

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.


2021 ◽  
Vol 10 (1) ◽  
pp. 06-13
Author(s):  
Viol Dhea Kharisma ◽  
Arif Nur Muhammad Ansori ◽  
Gabrielle Ann Villar Posa ◽  
Wahyu Choirur Rizky ◽  
Sofy Permana ◽  
...  

Acquired immune deficiency syndrome (AIDS) has been identified from US patients since 1981. AIDS is caused by infection with the human immunodeficiency virus type 1 (HIV-1) which is a retrovirus. HIV-1 gp120 can be recognized by the immune system because it is located outside the virion. The conserved region is identified in gp120, and it is recognized by an immune cell which then initiates specific immune responses, viral mutation escape, and increase vaccine protection coverage, a benefit derived from the conserved region-based vaccine design. However, previous researchers have little knowledge on this conserved region as a target for vaccine design. This paper explains how the conserved region of gp120 HIV-1 is a major target for vaccine design through a bioinformatics approach. The conserved region from gp120 was explored as a vaccine design target with a bioinformatics tool that consists of B-cell epitope mapping, vaccine properties, molecular docking, and dynamic simulation. The peptide vaccine candidate of B5 with the gp120 HIV-1 conserved region was found to provoke B-cell activation through a direct pathway, produce specific antibody, and increase protection from multi-strain viral infection.


2011 ◽  
Vol 55 (4) ◽  
pp. 247-253 ◽  
Author(s):  
Cheng-song Wan ◽  
Yong Zhou ◽  
Yang Yu ◽  
Li juan Peng ◽  
Wei Zhao ◽  
...  

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