Hepatitis C Virus Vaccine Development: A Step Forward

Author(s):  
Ahmed Atef Mesalam
2009 ◽  
Vol 11 (4) ◽  
pp. 313-325 ◽  
Author(s):  
Delphine Desjardins ◽  
Christophe Huret ◽  
Charlotte Dalba ◽  
Florian Kreppel ◽  
Stefan Kochanek ◽  
...  

2020 ◽  
Vol 71 (11) ◽  
pp. 2986-2990 ◽  
Author(s):  
Andrea Cox ◽  
Mark Sulkowski ◽  
Jeremy Sugarman

Abstract Despite the existence of established treatments for hepatitis C virus (HCV), more effective means of preventing infection, such as a vaccine, are arguably needed to help reduce substantial global morbidity and mortality. Given the expected challenges of developing such a vaccine among those at heightened risk of infection, controlled human infection studies seem to be a promising potential approach to HCV vaccine development, but they raise substantial ethical and practical concerns. In this article, we describe some of the challenges related to the possibility of using controlled human infection studies to accelerate HCV vaccine development. The related ethical and practical concerns require further deliberation before such studies are planned and implemented.


2016 ◽  
Vol 20 ◽  
pp. 55-63 ◽  
Author(s):  
Brian G Pierce ◽  
Zhen-Yong Keck ◽  
Steven KH Foung

2015 ◽  
Vol 2 (3) ◽  
pp. 285-295 ◽  
Author(s):  
Dapeng Li ◽  
Zhong Huang ◽  
Jin Zhong

Abstract Hepatitis C virus (HCV), an enveloped positive-sense single-stranded RNA virus, can cause chronic and end-stage liver diseases. Approximately 185 million people worldwide are infected with HCV. Tremendous progress has been achieved in the therapeutics of chronic hepatitis C thanks to the development of direct-acting antiviral agents (DAAs), but the worldwide use of these highly effective DAAs is limited due to their high treatment cost. In addition, drug-resistance mutations remain a potential problem as DAAs are becoming a standard therapy for chronic hepatitis C. Unfortunately, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health, and the worldwide eradication of HCV is critically dependent on an effective HCV vaccine. In this review, we summarize recent progresses on HCV vaccine development and present our views on the rationale and strategy to develop an effective HCV vaccine.


2021 ◽  
Author(s):  
Nicole E. Skinner ◽  
Clinton O. Ogega ◽  
Nicole Frumento ◽  
Kaitlyn E. Clark ◽  
Srinivasan Yegnasubramanian ◽  
...  

AbstractEarly development of broadly neutralizing antibodies (bNAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein E2 is associated with spontaneous clearance of infection, so induction of bNAbs is a major goal of HCV vaccine development. However, much remains to be learned at a molecular level about protective E2-reactive antibodies, since HCV infection persists in some individuals despite early development of broadly neutralizing plasma. To examine B cell repertoire features associated with broad neutralization and viral clearance, we performed RNA sequencing of the B cell receptors (BCRs) of HCV E2-reactive B cells of people with cleared or persistent HCV, including subjects with high or low plasma neutralizing breadth in both clearance and persistence groups. We identified many E2-reactive public BCR clonotypes, which are antibody clones with the same V and J-genes and identical CDR3 sequences, shared among subjects grouped by either clearance or neutralization status. The majority (89) of these public clonotypes were shared by two subjects with broad plasma neutralizing activity and cleared infection, but not found in subjects with high plasma neutralizing breadth and persistent infection. We cloned a potent, cross-reactive neutralizing monoclonal antibody (mAb) by pairing the most abundant public heavy and light chains from these two subjects, providing evidence that broadly E2-reactive public clonotypes arise in a subset of individuals with broadly neutralizing plasma and spontaneous clearance of infection. Further characterization of the molecular features and function of these antibodies can inform HCV vaccine development.


2008 ◽  
Vol 82 (12) ◽  
pp. 6067-6072 ◽  
Author(s):  
Zhen-Yong Keck ◽  
Oakley Olson ◽  
Meital Gal-Tanamy ◽  
Jinming Xia ◽  
Arvind H. Patel ◽  
...  

ABSTRACT A challenge in hepatitis C virus (HCV) vaccine development is defining conserved protective epitopes. A cluster of these epitopes comprises an immunodominant domain on the E2 glycoprotein, designated domain B. CBH-2 is a neutralizing human monoclonal antibody to a domain B epitope that is highly conserved. Alanine scanning demonstrated that the epitope involves residues G523, G530, and D535 that are also contact residues for E2 binding to CD81, a coreceptor required for virus entry into cells. However, another residue, located at position 431 and thus at a considerable distance in the linear sequence of E2, also contributes to the CBH-2 epitope. A single amino acid substitution at this residue results in escape from CBH-2-mediated neutralization in a genotype 1a virus. These results highlight the challenges inherent in developing HCV vaccines and show that an effective vaccine must induce antibodies to both conserved and more invariant epitopes to minimize virus escape.


Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 313
Author(s):  
Daniel Sepulveda-Crespo ◽  
Salvador Resino ◽  
Isidoro Martinez

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant.


Vaccine ◽  
2014 ◽  
Vol 32 (42) ◽  
pp. 5460-5467 ◽  
Author(s):  
Bethany White ◽  
Annie Madden ◽  
Maria Prins ◽  
Margaret Hellard ◽  
Handan Wand ◽  
...  

2008 ◽  
Vol 153 (6) ◽  
pp. 1021-1029 ◽  
Author(s):  
S.-H. Wei ◽  
W. Yin ◽  
Q.-X. An ◽  
Y.-F. Lei ◽  
X.-B. Hu ◽  
...  

2013 ◽  
Vol 145 (2) ◽  
pp. 285-288 ◽  
Author(s):  
Michael Houghton ◽  
John Lokman Law ◽  
D. Lorne Tyrrell

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