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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

Authors :
Sumana Chakravarty
Eric R. James
Tao Li
Kirsten E. Lyke
Abraham G. Eappen
Mario Roederer
Laura Novik
Adam Ruben
Uzma N. Sarwar
Anita Manoj
Sebastian A. Mikolajczak
Hope Decederfelt
Cynthia S. Hendel
Brandon K. Sack
Stefan H. I. Kappe
Pamela Costner
Matthew B. Laurens
Mary E. Enama
Adam DeZure
Niklas K. Björkström
Jay Noor
Lindsey S. Garver
Silas A. Davidson
Natasha K C
B. Kim Lee Sim
William R Whalen
Julie E. Ledgerwood
Stephen L. Hoffman
Barbara J. Flynn
Minglin Li
Andrew S. Ishizuka
Robert A. Seder
Martha Nason
Judith E. Epstein
Peter F. Billingsley
Lee-Jah Chang
Sarah H. Plummer
Ingelise J. Gordon
Christopher V. Plowe
Kailan Sierra-Davidson
Richard E. Stafford
Margaret A. Kemp
Barney S. Graham
Anusha Gunasekera
Kathryn L Zephir
Srinivas S. Rao
Thomas L. Richie
Tooba Murshedkar
LaSonji A. Holman
John Paul Todd
Floreliz Mendoza
Matthew Fishbaugher
Jamie G. Saunders
Andrea A. Berry
Gary A. Fahle
Geoffrey M. Lynn
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.

Details

ISSN :
1546170X
Volume :
22
Issue :
6
Database :
OpenAIRE
Journal :
Nature medicine
Accession number :
edsair.doi.dedup.....a718d82c493e141707776c75ccf0b084