Production and Formulation of Adenovirus Vectors

  • Nedim E. Altaras
  • John G. Aunins
  • Robert K. Evans
  • Amine Kamen
  • John O. KonzEmail author
  • Jayanthi J. Wolf
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 99)


Adenovirus vectors have attracted considerable interest over the past decade, with ongoing clinical development programs for applications ranging from replacement therapy for protein deficiencies to cancer therapeutics to prophylactic vaccines. Consequently, considerable product, process, analytical, and formulation development has been undertaken to support these programs. For example, “gutless” vectors have been developed in order to improve gene transfer capacity and durability of expression; new cell lines have been developed to minimize recombination events; production conditions have been optimized to improve volumetric productivities; analytical techniques and scaleable purification processes have advanced towards the goal of purified adenovirus becoming a “well-characterized biological”; and liquid formulations have been developed which maintain virus infectivity at 2–8°C for over 18 months. These and other advances in the production of adenovirus vectors are discussed in detail in this review. In addition, the needs for the next decade are highlighted.

Adenovirus Analytical characterization Cell culture Cell lines Formulation Purification 





adenovirus type 2


adenovirus type 5


anion exchange


adenovirus reference material


cytopathic effect


dissociation-enhanced flouroimmunoassay


enzyme-linked immunosorbent assay


good manufacturing practice


helper-dependent adenovirus


helper-dependent E1-positive particle


hours post-infection


multiplicity of infection


particle-to-infectivity ratio


plaque-forming unit


replication-competent adenovirus


reversed-phase high performance liquid chromatography


relative standard deviation


tissue culture infectious dose at 50%


quantitative polymerase chain reaction


viral particles


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We thank coworkers who contributed to the generation of unpublished data presented in this work (Fig. 2: Marie-Pierre Gentile and Gina Cremona; Fig. 4: Matthew Kalscheur, Marie-Pierre Gentile, and Benjamin Hughes; Figs. 8 and 9: Denise Nawrocki, Lynne Isopi, and Donna Williams) and Drs. Angelica Meneses-Acosta and Olivier Henry for providing data and assistance with Figs. 5 and 6. We also thank Dr. John Lewis and Dr. Katey Einterz Owen for reviewing portions of this manuscript and providing helpful suggestions.


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Authors and Affiliations

  • Nedim E. Altaras
    • 1
  • John G. Aunins
    • 1
  • Robert K. Evans
    • 2
    • 6
  • Amine Kamen
    • 5
  • John O. Konz
    • 3
    Email author
  • Jayanthi J. Wolf
    • 4
  1. 1.Fermentation and Cell CultureMerck Research LaboratoriesWest PointUSA
  2. 2.Vaccine Pharmaceutical ResearchMerck Research LaboratoriesWest PointUSA
  3. 3.Biologics Development and EngineeringMerck Research LaboratoriesWest PointUSA
  4. 4.Live Viral VectorsMerck Research LaboratoriesWest PointUSA
  5. 5.Biotech Research InstituteNational Research CouncilMontreal, QuebecCanada
  6. 6.VaxInnateCranburyUSA

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