Tolerogenic nanoparticles to induce immunologic tolerance: Prevention and reversal of FVIII inhibitor formation

Ai Hong Zhang, Robert J. Rossi, Jeongheon Yoon, Hong Wang, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


The immune response of hemophilia A patients to administered FVIII is a major complication that obviates this very therapy. We have recently described the use of synthetic, biodegradable nanoparticles carrying rapamycin and FVIII peptide antigens, to induce antigen-specific tolerance. Herein we test the tolerogenicity of nanoparticles that contains full length FVIII protein in hemophilia A mice, focusing on anti-FVIII humoral immune response. As expected, recipients of tolerogenic nanoparticles remained unresponsive to FVIII despite multiple challenges for up to 6 months. Furthermore, therapeutic treatments in FVIII-immunized mice with pre-existing anti-FVIII antibodies resulted in diminished antibody titers, albeit efficacy required longer therapy with the tolerogenic nanoparticles. Interestingly, durable FVIII-specific tolerance was also achieved in animals co-administered with FVIII admixed with nanoparticles encapsulating rapamycin alone. These results suggest that nanoparticles carrying rapamycin and FVIII can be employed to induce specific tolerance to prevent and even reverse inhibitor formation.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalCellular Immunology
StatePublished - 1 Mar 2016
Externally publishedYes


  • FVIII protein
  • Hemophilia A
  • Human
  • Immune tolerance
  • Nanoparticles
  • PLGA
  • Rapamycin


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