scholarly journals Novel monkey mAbs induced by a therapeutic vaccine targeting the hepatitis B surface antigen effectively suppress hepatitis B virus in mice

2021 ◽  
Author(s):  
Yuanzhi Chen ◽  
Xinchu Xiang ◽  
Ruoyao Qi ◽  
Yiwen Wang ◽  
Yang Huang ◽  
...  
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Therapeutic Vaccine ◽  
Physical Property ◽  
Cynomolgus Monkeys ◽  
Chimeric Antibodies ◽  
Hbsag Clearance ◽  
Alternative Approach

Abstract Background We have previously obtained a mouse anti-hepatitis B surface antigen (HBsAg) antibody E6F6 with long-lasting serum HBsAg clearance effects. The E6F6 epitope-based protein CR-T3-SEQ13 (HBsAg aa 113–135) vaccination therapy in cynomolgus monkeys induced long-term polyclonal antibodies-mediated clearance of HBsAg in the HBV transgenic (HBV-Tg) mice. Methods We isolated monoclonal antibodies from CR-T3-SEQ13 vaccinated cynomolgus monkeys, compared their therapeutic effects with E6F6, identified their epitopes on HBsAg, determined the pharmacokinetics, and studied their physical property. Results A panel of anti-HBsAg mAbs was generated through memory B cell stimulatory culture. Two lead monkey-human chimeric antibodies, C1–23 and C3–23, effectively suppressed HBsAg and HBV DNA in HBV-Tg mice. The humanized antibodies and humanized-mouse reverse chimeric antibodies of two antibodies exhibited comparable HBsAg clearance and viral suppression efficacy as those versions of E6F6 in HBV-Tg mice. Humanized antibody hu1–23 exhibited more efficacy HBsAg-suppressing effects than huE6F6–1 and hu3–23 in HBV-Tg mice at dose levels of 10 mg/kg and 20 mg/kg. Evaluation of the binding sites indicates that the epitope recognized by hu1–23 is located in HBsAg aa 118–125 and 121–125 for hu3–23. Physical property study revealed that hu1–23 and hu3–23 are stable enough for further development as a drug candidate. Conclusions Our data suggest that the CR-T3-SEQ13 protein is a promising HBV therapeutic vaccine candidate; and hu1–23 and hu3–23 are therapeutic candidates for the treatment of CHB. Moreover, the generation of antibodies from the epitope-based vaccinated subjects may be an alternative approach for novel antibody drug discovery. Statement of Significance Cynomolgus monkey mAbs were generated from an HBsAg-epitope-based-protein vaccination through memory B cell stimulatory culture. The humanized antibodies can efficiently mediate HBsAg clearance in HBV-Tg mice and may serve as anti-HBsAg therapeutic candidates. Generation of mAbs from the epitope-based vaccinated subjects is an alternative approach for novel antibody discovery.

scholarly journals A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice

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 ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Antibody Response ◽  
B Cell ◽  
Surface Antigen ◽  
Therapeutic Vaccine ◽  
Cell Epitope ◽  
Hbv Infection ◽  
Core Antigen ◽  
Hbsag Clearance ◽  
B Cell Epitope

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.

scholarly journals Time to seroconversion of HBsAg to anti-HBs in individuals who lost HBsAg during follow-up

2016 ◽  
Vol 144 (12) ◽  
pp. 2648-2653 ◽  
Author(s):  
M. R. H. ROUSHAN ◽  
M. MOHAMMADPOUR ◽  
M. BAIANY ◽  
S. SOLEIMANI ◽  
A. BIJANI
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Liver Function Tests ◽  
Hbsag Clearance ◽  
Positive Antibody ◽  
B Virus ◽  
The Mean ◽  
Cumulative Probabilities

SUMMARYTo determine the time to appearance of antibody against hepatitis B surface antigen (anti-HBs) after clearance of hepatitis B surface antigen (HBsAg) in chronically infected individuals, we followed up 3963 cases with positive antibody against hepatitis B e antigen (anti-HBe) from 1991 to 2014. Of these, 101 (67 males, 34 females) lost HBsAg. These serocleared cases were checked every 6-month interval regarding HBsAg, anti-HBs, liver function tests, and liver sonography. Hepatitis B virus DNA was assessed at the time of seroclearance or the appearance of anti-HBs. The mean age of these patients at entry to this study was 34·4 ± 13 years. The mean follow-up duration until seroclearance of HBsAg was 6·6 ± 4·3 years. After the mean follow-up of 43·7 ± 45 months, anti-HBs appeared in 64 (63·4%) cases. The cumulative probabilities of anti-HBs appearance for 2, 5 and 10 years were 24·3%, 58% and 78·2%, respectively. The appearance of anti-HBs was associated with age ⩾35 years and seroclearance of HBsAg (hazard ratio 1·96, 95% confidence interval 1·32–3·38,P= 0·016) but not with sex. The results show that anti-HBs may develop in 78·2% of cases within 10 years of HBsAg clearance. Age ⩾35 years at HBsAg loss was associated with earlier development of anti-HBs.

Mapping of linear B-cell epitopes of hepatitis B surface antigen

1991 ◽  
Vol 142 (6) ◽  
pp. 461-467 ◽  
Author(s):  
P Coursaget ◽  
G Lesage ◽  
P Le Cann ◽  
V Mayelo ◽  
C Bourdil
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
B Cell Epitopes ◽  
Linear B

scholarly journals Association of Human Leukocyte Antigen Class I Polymorphism with Spontaneous Clearance of Hepatitis B Surface Antigen in Qidong Han Population

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Fengqin Miao ◽  
Hang Sun ◽  
Ning Pan ◽  
Jinhuan Xu ◽  
Jie Qiu ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hbv Infection ◽  
Class I ◽  
Spontaneous Clearance ◽  
Han Population ◽  
Hbsag Clearance

Aim. To investigate whether HLA class I polymorphisms could influence the clearance of hepatitis B surface antigen (HBsAg) in Qidong Han population.Methods. We genotyped HLA-A, -B, and -C loci of 448 individuals with HBV persistent infection and 140 persons with spontaneous clearance of HBsAg by polymerase chain reaction with sequencing based typing (PCR/SBT). All the individuals were unrelated males enrolled from Qidong Han population and were followed up for 10 years.Results. The frequency ofHLA-A*33:03:01Gwas increased in persistent HBV infection group (Pvalue is 0.028), while frequency ofHLA-B*13:01:01Gwas increased in HBsAg clearance group (Pvalue is 0.0004).Conclusion. These findings suggested that the host HLA class I polymorphism is an important factor in determining the outcomes of HBV infection.

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