Peptide Aggregation Induced Immunogenic Rupture (PAIIR)

Adv Sci (Weinh). 2022 Jul;9(21):e2105868. doi: 10.1002/advs.202105868. Epub 2022 May 22.


Immunogenic cell death (ICD) arises when cells are under stress, and their membranes are damaged. They release damage-associated molecular patterns (DAMPs) that stimulate and drive the type and magnitude of the immune response. In the presence of an antigen, DAMPs ride the longevity and efficacy of antigen-specific immunity. Yet, no tool can induce the controlled ICD with predictable results. A peptide-based tool, [II], is designed that aggregates in the cell and causes cell membrane damage, generates ICD and DAMPs release on various cell types, and hence can act as an adjuvant. An influenza vaccine is prepared by combining [II] with influenza hemagglutinin (HA) subunit antigens. The results show that [II] induced significantly higher HA-specific immunoglobulin G1 (IgG1) and IgG2a antibodies than HA-only immunized mice, while the peptide itself did not elicit antibodies. This paper demonstrates the first peptide-aggregation induced immunogenic rupture (PAIIR) approach as a vaccine adjuvant. PAIIR is a promising adjuvant with a high potential to promote universal protection upon influenza HA vaccination.

Keywords: damage-associated molecular patterns; immunogenic cell death; influenza vaccination; peptide aggregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Humans
  • Influenza Vaccines*
  • Influenza, Human*
  • Mice
  • Mice, Inbred BALB C
  • Peptides


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Peptides