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Instability of adenoviral vectors during transport and its implication for clinical studies

Nature Medicine volume 5, pages 955–957 (1999)Cite this article

The viability of biological pharmaceuticals such as viral vectors may vary substantially from the time of production to the time of administration. Considerable efforts have been made to develop specifications for the characterization of viral vectors after production; however, little is known of vector potency at the time of administration. Here we demonstrate how vector viability can be substantially reduced as a result of formulation and transport conditions. We analyzed the susceptibility of adenoviral vectors to pH variations, and determined conditions for formulation and transport to help maintain vector viability.

The number of adenoviral gene therapy trials has increased considerably in the past few years. By 1996, there were 170 gene therapy clinical trials registered with the NIH Recombinant DNA Advisory Committee (RAC) and only 15% (26) used adenoviral vectors (Office of Recombinant DNA Database, July, 1998). Since then, 91 additional gene therapy trials have been submitted and 32% (29) use adenoviral vectors. With this increase in the proportion of trials using adenoviral vectors, there has been a concomitant increase in demand for highly purified and well-characterized clinical-grade preparations. However, unlike traditional pharmaceuticals, the potency of biological drugs is often difficult to characterize stringently1. Quantity, for viral vectors, can refer to the total number of virions or the number of infectious units. An adenoviral infectious titer can vary as much as 1 × 102, depending on the assay and laboratory used to analyze it1. In that report1, a simple method for standardization of adenoviral vector titering was described. Along with other groups (FDA Gene Therapy Workshop, 1997), we suggested that viral particles be used as quantitative descriptors of adenoviral vectors; infectious titers were recommended only as qualitative descriptors.

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Figure 1: Effect of pH on adenoviral vector stability.
Figure 2: Protection of adenoviral vectors after 24 h of exposure to dry ice.

References

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Acknowledgements

We thank Quantum Biotechnologies for supplying the Adeno-GFP vector and for the many discussions on vector formulation. We also thank O'Brian Smith for his assistance in statistical analyses, M. Scarpa for discussions on titer pre- and post-shipping, and X. Wei and W. Li for their technical assistance. This work was supported in part by NIH grant MO1RR00188 GCRC of NCRR and NIH grant P50-58204 Spore of NCI.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, M.C. 3-2374, 1102 Bates, Suite 1170, Houston, 77030, Texas, USA

    Cassandra Nyberg-Hoffman & Estuardo Aguilar-Cordova

  2. Texas Children's Cancer Center, Baylor College of Medicine, M.C. 3-2374, 1102 Bates, Suite 1170, Houston, 77030, Texas, USA

    Cassandra Nyberg-Hoffman & Estuardo Aguilar-Cordova

  3. Department of Pediatrics, Baylor College of Medicine, M.C. 3-2374, 1102 Bates, Suite 1170, Houston, 77030, Texas, USA

    Estuardo Aguilar-Cordova

Authors
  1. Cassandra Nyberg-Hoffman
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  2. Estuardo Aguilar-Cordova
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Correspondence to Estuardo Aguilar-Cordova.

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Nyberg-Hoffman, C., Aguilar-Cordova, E. Instability of adenoviral vectors during transport and its implication for clinical studies. Nat Med 5, 955–957 (1999). https://doi.org/10.1038/11400

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