Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model

Yokokawa, Hiroshi; Higashino, Atsunori; Suzuki, Saori; Moriyama, Masaki; Nakamura, Noriko; Suzuki, Tomohiko; Suzuki, Ritsuro; Ishii, Koji; Kobiyama, Kouji; Ishii, Ken J.; Wakita, Takaji; Akari, Hirofumi; Kato, Takanobu

doi:10.1136/gutjnl-2016-312208

Cited by 37 publications

(27 citation statements)

References 27 publications

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“…Many antiviral vaccines are based on viral particles as vaccine antigens 15 , 16 and protect by their induction of neutralizing antibodies. The proof-of-concept for the immunogenicity of cell culture-derived inactivated HCV has been obtained in animal models 17 – 19 . However, in these studies, ultracentrifugation-based downstream processes (DSP) were employed for virus concentration and purification.…”

Section: Introductionmentioning

confidence: 99%

Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

Lothert

Offersgaard

Pihl

et al. 2020

Sci Rep

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There is a large unmet need for a prophylactic hepatitis C virus (HCV) vaccine to control the ongoing epidemic with this deadly pathogen. Many antiviral vaccines employ whole viruses as antigens. For HCV, this approach became feasible following the development of infectious cell culture systems for virus production. However, the lack of efficient downstream processes (DSP) for HCV purification poses a roadblock for the development of a whole virus vaccine. Using cell culture-derived genotype 1a HCV we developed a scalable and efficient DSP train, employing commonly used clarification and ultrafiltration techniques, followed by two membrane-based chromatography steps. For virus capture, steric exclusion chromatography using cellulose membranes was established, resulting in a virtually complete virus recovery with > 99% protein and 84% DNA depletion. Virus polishing was achieved by sulphated cellulose membrane adsorbers with ~ 50% virus recovery and > 99% protein and 90% DNA depletion. Additional nuclease digestion resulted in 99% overall DNA depletion with final DNA concentrations of 2 ng/mL. Process results were comparable for cell culture-derived HCV of another major genotype (5a). This study provides proof-of-concept for establishment of an efficient and economically attractive DSP with potential application for production of an inactivated whole virus vaccine against HCV for human use.

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Section: Introductionmentioning

confidence: 99%

Development of a downstream process for the production of an inactivated whole hepatitis C virus vaccine

Lothert

Offersgaard

Pihl

et al. 2020

Sci Rep

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“…Since optimized mRNAs are continually existing in the cytosol, mRNA vaccines are being applied in diseaserelated immunotherapy. mRNAs are translated into corresponding antigens after being inoculated into host cells, imitating virus-infection-like humoral immunity and cellular immunity [62,63]. The nature of the corresponding antigens is an immune response-inducing antigen.…”

Section: Mechanisms Of Mrna Vaccine-mediated Immunotherapymentioning

confidence: 99%

mRNA vaccine: a potential therapeutic strategy

Wei¹,

et al. 2021

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AbstractmRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

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“…[101][102][103] Despite these challenges, a number of investigations have demonstrated success in preclinical animal studies showing induction of both humoral and cellular immunity against HCV. 104,105 Although promising preliminary results had been demonstrated in trials conducted in humans based in part on these finding, 106 in a phase II human clinical trial (ClinicalTrials.gov NCT01296451), these candidates were not found to be effective in preventing chronic HCV infection in adults. 107 Ultimately, the path to a successful preventative vaccine requires comprehensive evaluation of all aspects of protective immunity, innovative application of state-of-theart vaccine technology, and properly designed clinical trials that can affirm definitive endpoints of safety and efficacy.…”

Section: Small Scale Effortsmentioning

confidence: 99%