Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

J Pharm Sci. 2016 May;105(5):1567-1575. doi: 10.1016/j.xphs.2016.02.031. Epub 2016 Apr 1.


The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule, and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review, we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.

Keywords: immunogenicity; in vivo models; protein aggregation.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibody Formation / genetics*
  • Antibody Formation / immunology*
  • Humans
  • Immunogenetic Phenomena / physiology*
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoproteins / genetics*
  • Immunoproteins / immunology*
  • Mice
  • Mice, Transgenic
  • Models, Animal*
  • Protein Aggregates / genetics
  • Protein Aggregates / immunology
  • Species Specificity


  • Immunoglobulin G
  • Immunoproteins
  • Protein Aggregates