期刊
NATURE MEDICINE
卷 22, 期 6, 页码 614-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4110
关键词
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资金
- VRC, NIAID, NIH
- NIAID [5R44AI055229-11, 5R44AI058499-08, 5R44AI058375-08]
- Bill and Melinda Gates Foundation [24922]
- [6000.RADI.F.A0309]
- Novo Nordisk Fonden [NNF14OC0009347] Funding Source: researchfish
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 x 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-g-producing CD8 T cells were present at similar to 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.
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