A Natural Peptide Antigen within the Plasmodium Ribosomal Protein RPL6 Confers Liver TRM Cell-Mediated Immunity against Malaria in Mice

Cell Host Microbe. 2020 Jun 10;27(6):950-962.e7. doi: 10.1016/j.chom.2020.04.010. Epub 2020 May 11.

Abstract

Liver-resident memory CD8+ T (TRM) cells remain in and constantly patrol the liver to elicit rapid immunity upon antigen encounter and can mediate efficient protection against liver-stage Plasmodium infection. This finding has prompted the development of immunization strategies where T cells are activated in the spleen and then trapped in the liver to form TRM cells. Here, we identify PbRPL6120-127, a H2-Kb-restricted epitope from the putative 60S ribosomal protein L6 (RPL6) of Plasmodium berghei ANKA, as an optimal antigen for endogenous liver TRM cell generation and protection against malaria. A single dose vaccination targeting RPL6 provided effective and prolonged sterilizing immunity against high dose sporozoite challenges. Expressed throughout the parasite life cycle, across Plasmodium species, and highly conserved, RPL6 exhibits strong translation potential as a vaccine candidate. This is further advocated by the identification of a broadly conserved, immunogenic HLA-A02:01-restricted epitope in P. falciparum RPL6.

Keywords: CD8 T cell; T cell memory; adaptive immmunity; antigen; dendritic cell targeting; epitope discovery; liver; malaria; tissue-resident memory T cell; vaccine.

MeSH terms

  • Animals
  • Anopheles
  • Antigens, Protozoan / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Dendritic Cells / immunology
  • Female
  • Immunity, Cellular / immunology*
  • Immunization
  • Immunologic Memory / immunology
  • Liver / immunology*
  • Liver / parasitology
  • Malaria / parasitology
  • Malaria Vaccines / immunology
  • Malaria, Falciparum / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptides / immunology*
  • Plasmodium berghei / immunology*
  • Ribosomal Proteins / immunology*
  • Sporozoites / immunology

Substances

  • Antigens, Protozoan
  • Malaria Vaccines
  • Peptides
  • Ribosomal Proteins
  • ribosomal protein L6