Received: 09 October 2026
Accepted: 12 October 2026
Published online: 30 October 2026
UDC: 615.371:616.98:579.841.93
DOI: 10.53511/pharmkaz.2026.5.8
Article type: Original Research Article
DEVELOPMENT OF AN INDUSTRIAL MANUFACTURING TECHNOLOGY FOR A RECOMBINANT VIRAL VECTOR VACCINE AGAINST HUMAN BRUCELLOSIS
Akhmetsadykov N.N.¹, Zikibayeva K.B.¹, Nurmukhambetova A.B.¹,
Imanbekova T.A.¹, Shanbayev B.U.¹, Abekova A.O.¹, Svanbayev A.A.¹,
Nurolda E.¹, Rakhim M.A.¹, Zhaparkulova K.A.², Kossylganova A.E.²,
Atakanova A.A.², Mukhitdenova A.M.², Chervyakova O.V.³
¹ Scientific and Production Enterprise “Antigen” LLP, Abay, Almaty Region, Kazakhstan
² Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
³ Research Institute for Biological Safety Problems, National Holding “QazBioPharm”,
Gvardeisky, Zhambyl Region, Kazakhstan
Introduction. The development of recombinant viral vector vaccines requires reproducible and scalable manufacturing technologies that ensure the stability of critical process parameters and the quality attributes of the finished medicinal product. Despite significant progress in the development of candidate vaccines against human brucellosis, their industrial manufacturing processes remain insufficiently studied.
Aim. To develop and technologically substantiate an industrial manufacturing process for a recombinant viral vector vaccine against human brucellosis based on a recombinant capripoxvirus.
Materials and Methods. The study was conducted in 2025–2026 at the Scientific and Production Enterprise “Antigen” LLP (Almaty Region, Republic of Kazakhstan). Recombinant viruses rSPPV(TK-)OMP16 and rSPPV(TK-)OMP19/sodC, Vero cells, and a sequential culture scale-up system using CelCradle™ and TideXcell® bioreactors were employed. The developed manufacturing process included an upstream stage for viral biomass production, tangential flow ultrafiltration, multimodal chromatographic purification using Capto™ Core 700 resin, production of the active pharmaceutical ingredient (API), and aseptic preparation of the finished dosage form. Process reproducibility was evaluated using data from three independent pilot-scale manufacturing batches by calculating the mean, standard deviation, and coefficient of variation.
Results. Sequential scale-up increased the Vero cell biomass from 1.5–2.0 × 10⁸ to 1.5–2.0 × 10¹⁰ cells. The infectious titers of the resulting viral biomass were 6.29 ± 0.19 and 6.53 ± 0.21 log TCID₅₀/mL for rSPPV(TK-)OMP16 and rSPPV(TK-)OMP19/ sodC, respectively. The coefficient of variation did not exceed 10% for most evaluated process parameters. Following chromatographic purification, residual DNA and residual protein levels were 5.0 ± 1.0 ng/dose and 18.0 ± 2.6 ng/dose, respectively. The infectious titer of the finished vaccine was 5.66 ± 0.08 log TCID₅₀/mL. The results confirmed the reproducibility of the developed manufacturing process and the stability of the principal quality attributes across three pilot-scale batches.
Discussion. The results showed that the selected scale-up strategy enabled stable production of the required cell and viral biomass during transition to pilot-scale manufacturing. The combination of tangential flow ultrafiltration and multimodal chromatography reduced residual DNA and protein levels while preserving the infectivity of the viral vector. The reproducibility of the main process parameters across three batches supports the further scale-up of the developed manufacturing process.
Conclusion. An integrated and scalable manufacturing technology for a recombinant viral vector vaccine against human brucellosis was developed, encompassing Vero cell cultivation, viral vector replication, API production and purification, and preparation of the finished dosage form. The developed process may provide a technological basis for further industrial manufacturing and subsequent preclinical evaluation of the vaccine.
Keywords: brucellosis, recombinant viral vector vaccine, capripoxvirus, Vero cells, bioreactors, active pharmaceutical ingredient, tangential flow ultrafiltration, multimodal chromatography, scale-up, industrial manufacturing.
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