Ethical and Practical Issues Associated With the Possibility of Using Controlled Human Infection Trials in Developing a Hepatitis C Virus Vaccine

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.

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Recombinant retrovirus-like particle forming DNA vaccines in prime-boost immunization and their use for hepatitis C virus vaccine development

The Journal of Gene Medicine ◽

10.1002/jgm.1307 ◽

2009 ◽

Vol 11 (4) ◽

pp. 313-325 ◽

Cited By ~ 27

Author(s):

Delphine Desjardins ◽

Christophe Huret ◽

Charlotte Dalba ◽

Florian Kreppel ◽

Stefan Kochanek ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Vaccine ◽

Vaccine Development ◽

Dna Vaccines ◽

Boost Immunization

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Hepatitis C Virus Vaccine Development: A Step Forward

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa644 ◽

2020 ◽

Author(s):

Ahmed Atef Mesalam

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Vaccine ◽

Vaccine Development

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Viral evasion and challenges of hepatitis C virus vaccine development

Current Opinion in Virology ◽

10.1016/j.coviro.2016.09.004 ◽

2016 ◽

Vol 20 ◽

pp. 55-63 ◽

Cited By ~ 28

Author(s):

Brian G Pierce ◽

Zhen-Yong Keck ◽

Steven KH Foung

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Vaccine ◽

Vaccine Development ◽

Viral Evasion

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Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up

Viruses ◽

10.3390/v13081596 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1596

Author(s):

Alex S. Hartlage ◽

Amit Kapoor

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Development ◽

Human Infection ◽

Infection Model ◽

Vaccine Trials ◽

Viral Vaccine ◽

Chronic Hcv

Unless urgently needed to prevent a pandemic, the development of a viral vaccine should follow a rigorous scientific approach. Each vaccine candidate should be designed considering the in-depth knowledge of protective immunity, followed by preclinical studies to assess immunogenicity and safety, and lastly, the evaluation of selected vaccines in human clinical trials. The recently concluded first phase II clinical trial of a human hepatitis C virus (HCV) vaccine followed this approach. Still, despite promising preclinical results, it failed to protect against chronic infection, raising grave concerns about our understanding of protective immunity. This setback, combined with the lack of HCV animal models and availability of new highly effective antivirals, has fueled ongoing discussions of using a controlled human infection model (CHIM) to test new HCV vaccine candidates. Before taking on such an approach, however, we must carefully weigh all the ethical and health consequences of human infection in the absence of a complete understanding of HCV immunity and pathogenesis. We know that there are significant gaps in our knowledge of adaptive immunity necessary to prevent chronic HCV infection. This review discusses our current understanding of HCV immunity and the critical gaps that should be filled before embarking upon new HCV vaccine trials. We discuss the importance of T cells, neutralizing antibodies, and HCV genetic diversity. We address if and how the animal HCV-like viruses can be used for conceptualizing effective HCV vaccines and what we have learned so far from these HCV surrogates. Finally, we propose a logical but narrow path forward for HCV vaccine development.

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A Sustained Viral Response Is Associated With Reduced Liver-Related Morbidity and Mortality in Patients With Hepatitis C Virus

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2009.11.018 ◽

2010 ◽

Vol 8 (3) ◽

pp. 280-288.e1 ◽

Cited By ~ 221

Author(s):

Amit G. Singal ◽

Michael L. Volk ◽

Donald Jensen ◽

Adrian M. Di Bisceglie ◽

Philip S. Schoenfeld

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Viral Response ◽

Morbidity And Mortality ◽

Viral Response

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Hepatitis C virus vaccine development: old challenges and new opportunities

National Science Review ◽

10.1093/nsr/nwv040 ◽

2015 ◽

Vol 2 (3) ◽

pp. 285-295 ◽

Cited By ~ 20

Author(s):

Dapeng Li ◽

Zhong Huang ◽

Jin Zhong

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Vaccine Development ◽

Rna Virus ◽

Antiviral Agents ◽

Resistance Mutations ◽

Direct Acting Antiviral ◽

Direct Acting

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.

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Convergent antibody responses associated with broad neutralization of hepatitis C virus and clearance of infection

10.1101/2021.09.11.21263416 ◽

2021 ◽

Author(s):

Nicole E. Skinner ◽

Clinton O. Ogega ◽

Nicole Frumento ◽

Kaitlyn E. Clark ◽

Srinivasan Yegnasubramanian ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Early Development ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

High Plasma ◽

Spontaneous Clearance ◽

Cell Repertoire ◽

Molecular Features

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.

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Incidence of hepatitis C virus infection among Egyptian healthcare workers at high risk of infection

Journal of Clinical Virology ◽

10.1016/j.jcv.2013.01.005 ◽

2013 ◽

Vol 57 (1) ◽

pp. 24-28 ◽

Cited By ~ 13

Author(s):

Sayed F. Abdelwahab ◽

Mohamed Hashem ◽

Iman Galal ◽

Maha Sobhy ◽

Tamer S. Abdel-Ghaffar ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

High Risk ◽

Virus Infection ◽

Healthcare Workers ◽

Risk Of Infection ◽

Hepatitis C Virus Infection

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Hepatitis C Transmission after Prostate Biopsy

Case Reports in Urology ◽

10.1155/2013/797248 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Karim Ferhi ◽

Morgan Rouprêt ◽

Pierre Mozer ◽

Guillaume Ploussard ◽

Alain Haertig ◽

...

Keyword(s):

Prostate Cancer ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antibiotic Prophylaxis ◽

Prostate Biopsy ◽

Viral Transmission ◽

Risk Of Infection ◽

Ultrasound Probe ◽

Transrectal Prostate Biopsy ◽

A Current

Prostate biopsy is a current and well-codified procedure; antibiotic prophylaxis and rectal enema limit the risk of infection. To date, there has been no reported viral transmission between patients due to a contaminated ultrasound probe. In this study, we report the case of a patient who contracted the hepatitis C virus after transrectal prostate biopsy as part of an individual screening for prostate cancer.

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