Immunogenicity of Therapeutic Protein Aggregates

Ehab M. Moussa, Jainik P. Panchal, Balakrishnan S. Moorthy, Janice Blum, Marisa K. Joubert, Linda O. Narhi, Elizabeth M. Topp

Research output: Contribution to journalArticle

149 Scopus citations


Therapeutic proteins have a propensity for aggregation during manufacturing, shipping, and storage. The presence of aggregates in protein drug products can induce adverse immune responses in patients that may affect safety and efficacy, and so it is of concern to both manufacturers and regulatory agencies. In this vein, there is a lack of understanding of the physicochemical determinants of immunological responses and a lack of standardized analytical methods to survey the molecular properties of aggregates associated with immune activation. In this review, we provide an overview of the basic immune mechanisms in the context of interactions with protein aggregates. We then critically examine the literature with emphasis on the underlying immune mechanisms as they relate to aggregate properties. Finally, we highlight the gaps in our current understanding of this issue and offer recommendations for future research.

Original languageEnglish (US)
Pages (from-to)417-430
Number of pages14
JournalJournal of Pharmaceutical Sciences
Issue number2
StatePublished - Feb 1 2016


  • immune response
  • physicochemical properties
  • protein aggregation
  • proteins
  • regulatory science

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Moussa, E. M., Panchal, J. P., Moorthy, B. S., Blum, J., Joubert, M. K., Narhi, L. O., & Topp, E. M. (2016). Immunogenicity of Therapeutic Protein Aggregates. Journal of Pharmaceutical Sciences, 105(2), 417-430.