Recombinant Albumin Enhances Lentiviral Vector Stability During Downstream Processing

Published on 26 May 2026

Poster

Lentiviral vectors (LVVs) remain one of the most widely used gene delivery systems for ex vivo cell therapy manufacturing, including CAR-T workflows, and are increasingly being explored for in vivo gene delivery applications. However, enveloped viral particles are highly sensitive to manufacturing-related stress during downstream processing.

Operations such as tangential flow filtration (TFF), sterile filtration, freeze-thaw cycling, and between-step process holds can contribute to cumulative vector loss through shear stress, surface adsorption, thermal degradation, and cryodamage. Across a full downstream process, these compounded losses can significantly reduce final infectious yield.

This poster evaluates how Optibumin® 25, InVitria’s recombinant human serum albumin (rHSA), supports lentiviral vector stability and infectious recovery across multiple downstream processing operations.

Why This Matters

Lentiviral vector manufacturing remains one of the largest cost drivers in cell and gene therapy production. Even modest improvements in infectious recovery during downstream processing can have a significant impact on:

• Functional vector yield
• Manufacturing efficiency
• Batch consistency
• Cost per dose
• Process scalability

Because LVVs are particularly sensitive to interfacial and thermal stress, stabilizing excipients that reduce adsorption and preserve particle integrity may help improve cumulative process recovery.

Experimental Overview

The poster evaluated Optibumin 25 across four common lentiviral vector downstream processing stress conditions:

• Tangential flow filtration (TFF)
• Process hold conditions at room temperature and 4 °C
• Freeze-thaw cryopreservation
• 0.2 µm sterile filtration

VSV-G pseudotyped lentiviral vectors produced in HEK293 cells were analyzed using:

• Genomic titer measurements by RT-qPCR
• Infectious titer measurements using HT-1080 transduction assays

The study compared buffer-only controls against formulations containing 1% recombinant human serum albumin.

Key Findings

Improved Lentiviral Recovery During TFF

During tangential flow filtration, Optibumin 25 supported higher vector retention and reduced permeate loss.

Observed results included:

• Approximately 1.5× higher infectious recovery
• Approximately 100× less virus lost to permeate
• Compatibility with common TFF cassette formats

The data is consistent with membrane passivation and reduced vector adsorption during filtration.

Application Note coming soon.  Subscribe to get notified.

Enhanced Stability During Freeze-Thaw

Cryopreservation studies demonstrated improved lentiviral vector recovery following freeze-thaw stress in the presence of recombinant albumin.

Key observations included:

• Approximately 4× higher infectious recovery compared to buffer-only controls
• Genomic titer recovery comparable to no-freeze reference samples

These findings suggest recombinant albumin may help preserve envelope integrity and reduce cryodamage during storage and thawing.

Application Note coming soon.  Subscribe to get notified.

Protection During Process Holds

Lentiviral vectors are frequently exposed to room temperature or refrigerated hold conditions between manufacturing operations.

Compared to albumin-free controls, Optibumin 25 supported:

• Higher infectious titer retention
• Improved genomic titer preservation
• Improved stability at both room temperature and 4 °C

This may help reduce cumulative titer loss during extended downstream workflows.

Application Note coming soon.  Subscribe to get notified.

Reduced Loss During Sterile Filtration

Pre-conditioning 0.2 µm PES filters with recombinant albumin improved lentiviral vector recovery during sterile filtration.

The study demonstrated:

• Approximately 3× higher infectious recovery
• Improved genomic retention
• Effective filter passivation after only a short pre-treatment step

These results suggest recombinant albumin may help minimize vector adsorption during final sterile filtration operations.

Read more about this in the Application Note – Preserving Lentiviral Titer During Sterile Filtration Using Recombinant Albumin

Conclusion

One stabilizer. Multiple DSP failure modes addressed.

Optibumin 25 improved lentiviral vector recovery across TFF, freeze-thaw, process holds, and sterile filtration, helping preserve more infectious vector throughout downstream processing. The result is a more predictable manufacturing process with the potential for higher usable yield, lower variability, and reduced per-dose cost.

About Optibumin 25

Optibumin 25 is a recombinant human serum albumin manufactured in a non-mammalian expression system. The product is:

• Animal-origin-free
• Stabilizer-free
• Pasteurization-free
• Manufactured with high lot-to-lot consistency

Optibumin 25 has also been incorporated into approved biologic products, including ERVEBO®, supporting regulatory familiarity with recombinant albumin in enveloped vector applications.

Download the Poster

Learn more about how recombinant albumin can support lentiviral vector manufacturing workflows.