Identification of novel hepatitis B virus therapeutic vaccine candidates derived from polymerase protein

Zheng, Juzeng; Xia, Ziqiang; Xu, Yilun; Ou, Zhanfan; Lin, Xiuqing; Jin, Sisi; Liu, Yang; Wu, Jinming

doi:10.18632/aging.203053

Cited by 7 publications

(9 citation statements)

References 43 publications

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“…4B). The HL peptide has been reported numerous times in literature as an HLA-A02 binder [45][46][47] , thus it is likely in the training set of NetMHCpan4.1 and MHCflurry 2.0. We went on to check whether our StrB methods can identify the HG peptide as a binder.…”

Section: A Case Study: Vaccine For Chronic Hepatitis B Virus (Hbv) In...mentioning

confidence: 99%

“…4B). The HL peptide has been reported numerous times in literature as an HLA-A02 binder [43][44][45] , thus it is likely present in the training set of NetMHCpan4.1 and MHCflurry 2.0. In a blind test setting (i.e., we did not know the labels of binding or not beforehand when running our StrB methods), we went on to check whether our StrB methods can accurately identify the HL/HG peptides as binders.…”

Section: A Case Study: Vaccine For Chronic Hepatitis B Virus (Hbv) In...mentioning

confidence: 99%

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Improving generalizability for MHC-I binding peptide predictions through geometric deep learning

Marzella,

Crocioni,

Radusinovic

et al. 2023

Preprint

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Understanding the peptide presentation mechanism of Major Histocompatibility Complex (MHC) is crucial to study the recognition of pathogens, the treatment of autoimmune diseases and in developing cancer immunotherapies. To comprehend these mechanisms and design effective therapies at affordable costs, it is fundamental to be able to precisely predictin silicowhich peptides can be bound by each MHC. Many computational approaches have been developed to identify MHC-binding peptides based on their sequences, however, they present biases and their performance on less-studied MHC alleles with limited experimental binding data is severely restricted by their sequence-based (SeqB) nature. We reason that structure-based (StrB) methods could learn the physico-chemical and geometrical rules of peptide-MHC (pMHC) complexes conserved among the alleles, thus generalizing better. We designed three supervised StrB geometric deep learning (GDL) methods, showing superior generalization across all StrB methods over two SeqB methods when the test data is distant from the training data. To further explore data efficiency, we designed a novel self-supervised GDL approach trained only on ∼1K x-ray structures, 3D-SSL, which predicts binding affinities without seeing any during training. Finally, we showcase our StrB method on a case study from the HPV vaccine design to show how StrB methods are robust to biases in the binding data. These findings highlight the potentials of structure-based methods in efficiently utilizing limited data, enhancing generalizability. This study bears important implications on data hungry fields, for example, the long-standing T cell receptor (TCR) specificity challenge.

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Section: A Case Study: Vaccine For Chronic Hepatitis B Virus (Hbv) In...mentioning

confidence: 99%

Section: A Case Study: Vaccine For Chronic Hepatitis B Virus (Hbv) In...mentioning

confidence: 99%

Improving generalizability for MHC-I binding peptide predictions through geometric deep learning

Marzella,

Crocioni,

Radusinovic

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Researchers must select suitable prediction tools that best adapt their objectives. Different studies used this reverse vaccinology strategy in order to select the best in-class epitopes for different infectious diseases such as SARS-CoV-2 ( 104 ), Nipah virus ( 130 ), Leishmania ( 131 ), HBV ( 132 ), HIV ( 133 ), Influenza ( 134 ), Tuberculosis ( 135 ), Ebola virus ( 136 ), Neisseria ( 137 ), Plasmodium ( 138 ), Trypanosoma ( 139 ), or Chikungunya and Mayaro viruses ( 140 ).…”

Section: Epitope Mapping For DC Vaccine Developmentmentioning

confidence: 99%

Refining the DC-targeting vaccination for preventing emerging infectious diseases

Pastor

Ghazzaui²,

Hammoudi³

et al. 2022

Front. Immunol.

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The development of safe, long-term, effective vaccines is still a challenge for many infectious diseases. Thus, the search of new vaccine strategies and production platforms that allow rapidly and effectively responding against emerging or reemerging pathogens has become a priority in the last years. Targeting the antigens directly to dendritic cells (DCs) has emerged as a new approach to enhance the immune response after vaccination. This strategy is based on the fusion of the antigens of choice to monoclonal antibodies directed against specific DC surface receptors such as CD40. Since time is essential, in silico approaches are of high interest to select the most immunogenic and conserved epitopes to improve the T- and B-cells responses. The purpose of this review is to present the advances in DC vaccination, with special focus on DC targeting vaccines and epitope mapping strategies and provide a new framework for improving vaccine responses against infectious diseases.

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“…On the contrary, CHB is characterized with immune tolerance and exhaustion of HBV specific T-cells. Thus, overcoming immune tolerance during CHB has become the fundament for the development of HBV therapeutic vaccine [9], which aims to endeavor the enhancement of immune response by providing non-infective HBV antigen during CHB infection [10].…”

Section: Introductionmentioning

confidence: 99%

Cloning and Expression of HBcAg Using Food Grade Vector pNZ8149 in Lactococcus Lactis for the Development of HBV Therapeutic Vaccine

Umami¹,

Anwar²,

Murtiyaningsih³

et al. 2023

Proceedings of the 1st International Conference for Health Research – BRIN (ICHR 2022)

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Hepatitis B virus (HBV) infection remains a major cause of chronic liver diseases which may develop into cirrhosis and hepatocellular carcinoma (HCC). Although HBV prophylactic vaccine is available, currently there is no complete cure for chronic hepatitis B (CHB). One of the alternatives for CHB treatment is therapeutic vaccine. The HBV core antigen (HBcAg) becomes a suitable candidate for HBV therapeutic vaccine since it is known as a potent inducer of B-cell and T-cell responses. In this study, we report the development of HBV therapeutic vaccine by expressing HBcAg derived from HBV subgenotype B3, which is one of the predominant sub-genotypes in Indonesia. A food grade expression vector pNZ8149 which contains nisin-controlled gene as an inducible promoter, was used to express HBcAg in Lactococcus lactis NZ3900. Moreover, signal peptide usp45 was added in the N-terminal of the gene of interest to increase protein secretion efficiency. The native HBV core gene was synthesized and successfully cloned into plasmid pNZ8149 and transformed into Lactococcus lactis NZ3900 using lactose as a selection marker. The expression of HBcAg was induced using 10 ng/mL nisin and confirmed using dot blot hybridization analysis. Finally, the target protein which is 21 kDa in size was obtained by partial purification using size exclusion chromatography. In conclusion, HBcAg was successfully cloned and expressed using a food grade expression vector pNZ8149 in Lactococcus lactis NZ3900. These findings will pave the development of therapeutic vaccine for CHB treatment in the future.

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Identification of novel hepatitis B virus therapeutic vaccine candidates derived from polymerase protein

Cited by 7 publications

References 43 publications

Improving generalizability for MHC-I binding peptide predictions through geometric deep learning

Improving generalizability for MHC-I binding peptide predictions through geometric deep learning

Refining the DC-targeting vaccination for preventing emerging infectious diseases

Cloning and Expression of HBcAg Using Food Grade Vector pNZ8149 in Lactococcus Lactis for the Development of HBV Therapeutic Vaccine

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