An Inactivated Hepatitis C Virus Vaccine on the Horizon?

Houghton, Michael; Law, John Lok Man; Tyrrell, D. Lorne

doi:10.1053/j.gastro.2013.06.029

Cited by 8 publications

(7 citation statements)

References 22 publications

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“…As more patients with HCV infection are treated, isolation rooms could eventually disappear. In any case, the main objective should be to develop a vaccine that is effective against HCV [39,40,41]. …”

Section: Discussionmentioning

confidence: 99%

Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4

Abad¹,

Vega²,

Hernández³

et al. 2017

Am J Nephrol

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Background: Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals. Methods: This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously. Results: Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions. Conclusion: A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.

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Section: Discussionmentioning

confidence: 99%

Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4

Abad¹,

Vega²,

Hernández³

et al. 2017

Am J Nephrol

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“…These unique characteristics, as well as the reduced concentration of non-HCV proteins in serum-free culture supernatants, are expected to facilitate generation of purified and concentrated virus stocks, required for vaccine development and biophysical studies of HCV particle composition [54–57]. Further, the developed serum-free culture conditions might reduce the risk of contamination with adventitious microbial agents in future vaccine antigen preparations [40,41]. …”

Section: Discussionmentioning

confidence: 99%

“…This is expected to be facilitated by reducing concentrations of non-HCV proteins such as FBS derived proteins in HCVcc producing cell cultures. Further, use of FBS and animal-derived trypsin increases the risk of contamination with adventitious microbial agents, of relevance for HCV vaccine development [40,41]. Thus, development of methods for production of HCVcc under serum-free conditions is a research focus.…”

Section: Introductionmentioning

confidence: 99%

Production and characterization of high-titer serum-free cell culture grown hepatitis C virus particles of genotype 1–6

et al. 2014

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Recently, cell culture systems producing hepatitis C virus particles (HCVcc) were developed. Establishment of serum-free culture conditions is expected to facilitate development of a whole-virus inactivated HCV vaccine. We describe generation of genotype 1–6 serum-free HCVcc (sf-HCVcc) from Huh7.5 hepatoma cells cultured in adenovirus expression medium. Compared to HCVcc, sf-HCVcc showed 0.6 to 2.1 log10 higher infectivity titers (4.7–6.2 log10 Focus Forming Units/mL), possibly due to increased release and specific infectivity of sf-HCVcc. In contrast to HCVcc, sf-HCVcc had a homogeneous single-peak density profile. Entry of sf-HCVcc depended on HCV co-receptors CD81, LDLr, and SR-BI, and clathrin-mediated endocytosis. HCVcc and sf-HCVcc were neutralized similarly by chronic-phase patient sera and by human monoclonal antibodies targeting conformational epitopes. Thus, we developed serum-free culture systems producing high-titer single-density sf-HCVcc, showing similar biological properties as HCVcc. This methodology has the potential to advance HCV vaccine development and to facilitate biophysical studies of HCV.

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“…En la medida en la que se vayan tratando la mayoría de los pacientes con infección VHC, es posible que las salas de aislamiento para pacientes con VHC tiendan a desaparecer. En cualquier caso, el desarrollo de una vacuna eficaz frente al VHC debe ser el objetivo definitivo [35][36][37] .…”

Section: Discussionunclassified

Eficacia de los antivirales de acción directa en la infección por el virus de la hepatitis C en pacientes en hemodiálisis

et al. 2017

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Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3±7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.

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An Inactivated Hepatitis C Virus Vaccine on the Horizon?

Cited by 8 publications

References 22 publications

Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4

Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4

Production and characterization of high-titer serum-free cell culture grown hepatitis C virus particles of genotype 1–6

Eficacia de los antivirales de acción directa en la infección por el virus de la hepatitis C en pacientes en hemodiálisis

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