How improved virus purification and smarter analytics can contribute to the future of vaccines and biotech

AUTHORS

Johanna Bacher, Leo A. Jakob, Tomas Mesurado, Narges Lali, Alexander Zollner, Alois Jungbauer, Patricia Pereira Aguilar, Viktoria Mayer, Florian Steiner 

In the race for better and safer biopharmaceuticals and viral therapies, two things determine success or failure: how well we can purify viruses and virus-like particles (VLPs)–and how precisely can we measure them. Two recent scientific papers shed light on these challenges from complementary angles:
  • One study shows how highly pure, infectious measles viruses can be produced efficiently.
  • The second paper investigates how host cell DNA and chromatin distort the analysis of VLPs – and why this is an underestimated issue in research and manufacturing.

Taken together, they paint a picture of how important it is to control impurities at every level – from research to industrial manufacturing.

The challenge: viruses & VLPs are sensitive – and their impurities are tricky

Modern biomedical applications use viruses and virus-like particles in many ways: as vaccines, as vectors for gene therapy, or even as oncolytic viruses that selectively destroy tumor cells. However, both viruses and VLPs are sensitive bionanoparticles whose function depends strongly on how clean they are and how well they are characterized.

Both publications point out, however, that DNA, especially in the form ofchromatin, is among the most critical impurities. They resemble viruses/VLPs in size, shape, and charge – and are therefore easily co-purified. This can lead to false analytical values because VLPs and chromatin elute in a similar size range; yields may also be calculated incorrectly because purity is insufficient. Without thorough removal of these impurities, even the best analytics are only reliable to a limited extent.

Efficient production of highly pure measles viruses

The second publication takes the decisive step further: it shows how DNA and chromatin can be practically eliminated – thereby massively increasing purity. The researchers tested heparin-based affinity chromatography methods and combined them with two endonucleases for comparison:
  • Benzonase®, a traditional and commonly used endonuclease
  • MSAN, a salt-active nuclease that remains effective even at high salt concentrations
The combination of MSAN and heparin chromatography proved particularly promising, achieving a 62% yield with extremely low residual DNA levels. The process also meets modern regulatory requirements and, due to its good scalability, is well suited for industrial manufacturing.

Benefits of the findings

These developments are far more than minor technical improvements. They enable faster vaccine development: higher purity and reliable analytics allow new vaccine candidates to be assessed more quickly while meeting strict international requirements. Combining the insights from both studies makes one thing clear: Analytics and purification are inseparably linked.
  • Without good analytics, you don’t know what the product actually contains.
  • Without good purification, analytics remain unreliable.

With salt-active nucleases such as MSAN and optimized analytics, new high-performance process chains are emerging – making the entire spectrum of modern viral technologies safer, faster, and more efficient.

These papers therefore lay an important foundation for future vaccines, cancer therapies, and innovative biopharmaceuticals that will directly benefit society.

Highly pure measles virus generated by combination of salt-active nuclease treatment and heparin affinity chromatography
Impact of Host Cell DNA and Chromatin on Virus-like Particle Analysis by Light Scattering in Asymmetrical Flow Field-flow Fractionation