New strategies in downstream processing optimization for enveloped viruses

PhD Seminars

Title: New strategies in downstream processing optimization for enveloped viruses: exploiting the fundamentals

Speaker: Tiago Vicente

Laboratory: Animal Cell Technology

Abstract
Over the last two decades, the potential of viruses for application in gene therapy and vaccination
brought new challenges in bioprocessing development. Particularly, the downstream processing
of enveloped viruses urges a shift from bench-scale towards robust, scalable and cost-effective
strategies to produce clinical grade viral vectors. Enveloped viruses constitute an important class
of vectors holding great potential in clinical applications; however, their biological complexity
and the need for preserving their infectivity/”bioactivity” as biopharmaceutical products lead to
different process bottlenecks. A more sound, knowledgeable approach to identify the critical
points defining the process hurdles was the starting point to address the optimization of the stateof-
the-art downstream process steps.
We have developed a scale-down model strategy on the utilization of surface plasmon resonance
(SPR) spectroscopy into an analytical, pseudo-chromatography tool for the measurement of the
sorption and ion-exchange phenomena. In this work, recombinant baculoviruses – currently
highly promising enveloped viral vectors for human gene therapy and vaccination – served as
model particles. The analysis of the adsorption/desorption behavior of the baculovirus system
split into three cuts – the product (the infective baculovirus), the main product-related impurities,
and the main process-related impurities – provided a broad prediction of the adsorption
capacities at given equilibration conditions onto an ion-exchange surface, useful in
multicomponent analysis on an ion-exchange chromatography step.
Studies based on ζ potential measured through dynamic light scattering also yielded important
conclusions concerning the interaction free energies of the different components of this viral
vector challenged to an ion-exchange matrix.
The current ion-exchange purification strategy can now be optimized benefiting from these
innovative insights. This strategy may become a cost-effective tool in process design and
development for biopharmaceuticals as virus-like particles or other viral vectors.
 

Short-CV

2000 to 2005 – Degree in Biological Engineering at Instituto Superior Técnico, Universidade
Técnica de Lisboa; Trainee at Novartis Institutes for BioMedical Research, Basel, Switzerland
(March to September, 2005)
2005 to 2006 – Grant holder (BI) in the Cell Division at IGC. Supervision: Dr. Álvaro Tavares.
2007 to present - PhD student in the Animal Cell Technology Unit at IBET/ITQB-UNL.
Supervision: Dr Paula M. Alves and Professor Manuel J. T. Carrondo