Protection against malaria at 1 year and immune correlates following PfSPZ vaccination

Nat Med. 2016 Jun;22(6):614-23. doi: 10.1038/nm.4110. Epub 2016 May 9.


An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 × 10(5) PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21-25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon-γ-producing CD8 T cells were present at ∼100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.

Publication types

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

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Protozoan / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Healthy Volunteers
  • Humans
  • Immunogenicity, Vaccine / immunology*
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology
  • Liver / cytology
  • Liver / immunology*
  • Macaca mulatta
  • Malaria Vaccines / immunology
  • Malaria Vaccines / therapeutic use*
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Parasitemia / immunology
  • Parasitemia / prevention & control*
  • Plasmodium falciparum / immunology*
  • Sporozoites / immunology
  • T-Lymphocytes / immunology
  • Young Adult


  • Antibodies, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Interferon-gamma