GMP manufacturing of Vvax001, a therapeutic anti-HPV vaccine based on recombinant viral particlesJorritsma-Smit, A., van Zanten, C. J., Schoemaker, J., Meulenberg, J. J. M., Touw, D. J., Kosterink, J. G. W., Nijman, H. W., Daemen, T. & Allersma, D. P., 15-Feb-2020, In : European Journal of Pharmaceutical Sciences. 143, 8 p., 105096.
Research output: Contribution to journal › Article › Academic › peer-review
- Pharmaceutical Analysis
- Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
- Groningen Research Institute for Asthma and COPD (GRIAC)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Pharmacokinetics, Toxicology and Targeting
- PharmacoTherapy, Epidemiology and Economics
- Targeted Gynaecologic Oncology (TARGON)
- Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Pharmacotherapy and Pharmaceutical Care
- Translational Immunology Groningen (TRIGR)
- Microbes in Health and Disease (MHD)
Therapeutic vaccination is being explored as a treatment strategy for the treatment of patients with primary or metastatic tumours. We developed a vaccine targeted to Human papillomavirus (HPV)-induced tumours based on recombinant Semliki Forest virus (rSFV) encoding a fusion protein of the E6 and E7 proteins of HPV type 16. To enable a phase I clinical trial with this vaccine, Vvax001, a Good Manufacturing Practice (GMP)-compliant manufacturing process was set up and clinical material was produced.
Upstream production of the clinical material resulted in viral titers from 2.4 x 10(7) to 1.3 x 10(9) infectious particles/ mL in the harvest. The total volume of 6.0 liter crude virus was purified in 13 consecutive downstream purification runs. The mean titer after purification was 4.0 x 10(8) infectious particles/mL and the mean recovery was 19%. Finally, clinical material was filled at a target concentration of 1.25 x 10(8) infectious particles/mL. Release testing included tests for viral titer and virus identity, biological activity, sterility, bacterial endotoxins, adventitious viruses and absence of replication competent virus. The product complied with all specifications and was released for use as an investigational medicinal product.
This is the first GMP production process developed for a SFV-based therapeutic vaccine. The vaccine, Vvax001 is targeted to HPV and has shown promising results in preclinical studies. The GMP-produced Vvax001 material met the quality criteria and was of sufficient quantity to enable assessment of its immunogenicity, safety and efficacy in a clinical setting.
|Number of pages||8|
|Journal||European Journal of Pharmaceutical Sciences|
|Early online date||25-Oct-2019|
|Publication status||Published - 15-Feb-2020|
- GMP, ATMP, Semliki Forest Virus, recombinant viral particles, vaccine, Human Papilloma Virus, SEMLIKI-FOREST-VIRUS, HUMAN-PAPILLOMAVIRUS, FUSION PROTEIN, IMMUNIZATION, INFECTION, EFFICACY, CANCERS, CELLS, MODEL, E6