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Protection against malaria at 1 year and immune correlates following PfSPZ vaccination
Protection against malaria at 1 year and immune correlates following PfSPZ vaccination
- Source :
- Nature medicine. 22(6)
- Publication Year :
- 2016
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Adult
Male
Adolescent
T cell
T-Lymphocytes
Plasmodium falciparum
Antibodies, Protozoan
Enzyme-Linked Immunosorbent Assay
Parasitemia
CD8-Positive T-Lymphocytes
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Interferon-gamma
Young Adult
Immunogenicity, Vaccine
parasitic diseases
Malaria Vaccines
medicine
Cytotoxic T cell
Animals
Humans
Malaria, Falciparum
biology
business.industry
General Medicine
Middle Aged
medicine.disease
biology.organism_classification
Macaca mulatta
PfSPZ vaccine
Healthy Volunteers
Vaccination
030104 developmental biology
medicine.anatomical_structure
Immunization
Liver
Sporozoites
Immunoglobulin G
Immunology
Administration, Intravenous
Female
business
Malaria
Subjects
Details
- ISSN :
- 1546170X
- Volume :
- 22
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....a718d82c493e141707776c75ccf0b084