A malaria vaccine adjuvant based on recombinant antigen binding to liposomes

Nat Nanotechnol. 2018 Dec;13(12):1174-1181. doi: 10.1038/s41565-018-0271-3. Epub 2018 Oct 8.


Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its apparently limited immunogenicity in humans has hindered clinical development. Here, we show that recombinant, polyhistidine-tagged (his-tagged) Pfs25 can be mixed at the time of immunization with pre-formed liposomes containing cobalt porphyrin-phospholipid, resulting in spontaneous nanoliposome antigen particleization (SNAP). Antigens are stably presented in uniformly orientated display via his-tag insertion in the cobalt porphyrin-phospholipid bilayer, without covalent modification or disruption of antigen conformation. SNAP immunization of mice and rabbits is well tolerated with minimal local reactogenicity, and results in orders-of-magnitude higher functional antibody generation compared with other 'mix-and-inject' adjuvants. Serum-stable antigen binding during transit to draining lymph nodes leads to enhanced antigen uptake by phagocytic antigen-presenting cells, with subsequent generation of long-lived, antigen-specific plasma cells. Seamless multiplexing with four additional his-tagged Plasmodium falciparum polypeptides induces strong and balanced antibody production, illustrating the simplicity of developing multistage particulate vaccines with SNAP immunization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibody Formation
  • Antigens, Protozoan / administration & dosage
  • Antigens, Protozoan / immunology*
  • Female
  • Humans
  • Immunization
  • Liposomes / administration & dosage
  • Liposomes / immunology*
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control*
  • Mice
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / administration & dosage
  • Protozoan Proteins / immunology*
  • RAW 264.7 Cells
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology


  • Adjuvants, Immunologic
  • Antigens, Protozoan
  • Liposomes
  • Malaria Vaccines
  • Pfs25 protein, Plasmodium falciparum
  • Protozoan Proteins
  • Recombinant Proteins