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

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

Author information

1
Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (NIH), Maryland, USA.
2
Institute for Global Health, Center for Vaccine Development and Division of Malaria Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
3
Sanaria Inc., Rockville, Maryland, USA.
4
Protein Potential, LLC, Rockville, Maryland, USA.
5
Pharmaceutical Development Section, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
6
Naval Medical Research Center (NMRC), Malaria Department, Silver Spring, Maryland, USA.
7
Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
8
Center for Infectious Disease Research, Seattle, Washington, USA.
9
Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
10
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
11
Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

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.

PMID:
27158907
DOI:
10.1038/nm.4110
[Indexed for MEDLINE]

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