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GMP manufacturing of Vvax001, a therapeutic anti-HPV vaccine based on recombinant viral particles
Jorritsma-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
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GMP manufacturing of Vvax001, a therapeutic anti-HPV vaccine based on recombinant viral particles. / Jorritsma-Smit, Annelies; van Zanten, Coba J; Schoemaker, Jolande; Meulenberg, Janneke J M; Touw, Daan J; Kosterink, Jos G W; Nijman, Hans W; Daemen, Toos; Allersma, Derk P.
In: European Journal of Pharmaceutical Sciences, Vol. 143, 105096, 15.02.2020.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - GMP manufacturing of Vvax001, a therapeutic anti-HPV vaccine based on recombinant viral particles
AU - Jorritsma-Smit, Annelies
AU - van Zanten, Coba J
AU - Schoemaker, Jolande
AU - Meulenberg, Janneke J M
AU - Touw, Daan J
AU - Kosterink, Jos G W
AU - Nijman, Hans W
AU - Daemen, Toos
AU - Allersma, Derk P
N1 - Copyright © 2019. Published by Elsevier B.V.
PY - 2020/2/15
Y1 - 2020/2/15
N2 - 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 × 107 to 1.3 × 109 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 × 108 infectious particles/ mL and the mean recovery was 19%. Finally, clinical material was filled at a target concentration of 1.25 × 108 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.
AB - 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 × 107 to 1.3 × 109 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 × 108 infectious particles/ mL and the mean recovery was 19%. Finally, clinical material was filled at a target concentration of 1.25 × 108 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.
KW - GMP
KW - ATMP
KW - Semliki Forest Virus
KW - recombinant viral particles
KW - vaccine
KW - Human Papilloma Virus
KW - SEMLIKI-FOREST-VIRUS
KW - HUMAN-PAPILLOMAVIRUS
KW - FUSION PROTEIN
KW - IMMUNIZATION
KW - INFECTION
KW - EFFICACY
KW - CANCERS
KW - CELLS
KW - MODEL
KW - E6
U2 - 10.1016/j.ejps.2019.105096
DO - 10.1016/j.ejps.2019.105096
M3 - Article
C2 - 31669389
VL - 143
JO - European Journal of Pharmaceutical Sciences
JF - European Journal of Pharmaceutical Sciences
SN - 0928-0987
M1 - 105096
ER -
ID: 100909713