@article{d59c43045ad443f1a4edb7eddc47d70d,
title = "Protection against malaria at 1 year and immune correlates following PfSPZ vaccination",
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-I 3-producing CD8 T cells were present at {\^a} 1/4100-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.",
author = "Ishizuka, {Andrew S.} and Lyke, {Kirsten E.} and Adam DeZure and Berry, {Andrea A.} and Richie, {Thomas L.} and Mendoza, {Floreliz H.} and Enama, {Mary E.} and Gordon, {Ingelise J.} and Chang, {Lee Jah} and Sarwar, {Uzma N.} and Zephir, {Kathryn L.} and Holman, {Lasonji A.} and James, {Eric R.} and Billingsley, {Peter F.} and Anusha Gunasekera and Sumana Chakravarty and Anita Manoj and Minglin Li and Ruben, {Adam J.} and Tao Li and Eappen, {Abraham G.} and Stafford, {Richard E.} and Natasha, {K. C.} and Tooba Murshedkar and Hope DeCederfelt and Plummer, {Sarah H.} and Hendel, {Cynthia S.} and Laura Novik and Costner, {Pamela J.M.} and Saunders, {Jamie G.} and Laurens, {Matthew B.} and Plowe, {Christopher V.} and Barbara Flynn and Whalen, {William R.} and Todd, {J. P.} and Jay Noor and Srinivas Rao and Kailan Sierra-Davidson and Lynn, {Geoffrey M.} and Epstein, {Judith E.} and Kemp, {Margaret A.} and Fahle, {Gary A.} and Mikolajczak, {Sebastian A.} and Matthew Fishbaugher and Sack, {Brandon K.} and Kappe, {Stefan H.I.} and Davidson, {Silas A.} and Garver, {Lindsey S.} and Bj{\"o}rkstr{\"o}m, {Niklas K.} and Nason, {Martha C.} and Graham, {Barney S.} and Mario Roederer and {Kim Lee Sim}, B. and Hoffman, {Stephen L.} and Ledgerwood, {Julie E.} and Seder, {Robert A.}",
note = "Funding Information: The authors thank the vaccine trials participants for their contribution and commitment to vaccine research. We acknowledge the contributions of: our US National Institutes of Health (NIH) Clinical Center (CC) and National Institute of Allergy and Infectious Diseases (NIAID) colleagues, especially J. Stein, J. Pierson, R. Eckes, P. Driscoll, L. Ediger, and the nursing staff of the 5NW, SCSU, 5SE-S, and 5SE-N units; our VRC colleagues, especially A. Mittelman, H. Harvey, M. Young, C. Artis, R. Hicks, P. Darrah, and T. Abram; our Sanaria and Protein Potential colleagues, especially Y. Abebe, J. Jackson, A. Awe, M. King, H. Huang, A. Patil, S. Matheny, J. Overby, Y. Wen, K. Nelson, V. Pich, M. Orozco, D. Padilla, E. Saverino, B. Jiang, L. Gao, R. Xu, E. Fomumbod, M. Laskowski, T.T. Wai, F. Beams, R. Thompson, and A. Hoffman for administrative, operations, and legal support, and T. Luke for insight and inspiration; the EMMES Corporation; the NIAID Institutional Review Board; the NIAID Office of Communications and Government Relations; the NIH CC Department of Laboratory Medicine; the NIH CC IND Pharmacy, and the NIH CC Patient Recruitment and Public Liaison Office. We appreciate the expert reviews of the Safety Monitoring Committee (A. Durbin, K. Kester, and A. Cross) and the assistance from the US Military Malaria Vaccine Program, the Walter Reed Army Institute of Research Entomology Branch, and the Naval Medical Research Center (NMRC), especially A. Reyes, Y. Alcorta, G. Banania, C. Fedders, M. Dowler, T. Savransky, D. Patel, C. Brando, K. Kobylinski, and K. Walker. This work was supported by the intramural research program of the VRC, NIAID, NIH. Production and characterization of the PfSPZ Vaccine were supported in part by NIAID Small Business Innovation Research grants 5R44AI055229-11 (S.L.H.), 5R44AI058499-08 (S.L.H.), and 5R44AI058375-08 (S.L.H.). The humanized mouse experiments reported here were funded by the Bill and Melinda Gates Foundation (Investment ID: 24922; to S.H.I.K.). The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the funding agency or collaborators. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of the Army, the Department of Defense, or the US Government. This work was supported in part by work unit number 6000.RADI.F.A0309 to NMRC. J.E.E. and S.A.D. are military service members, and this work was prepared as part of their official duties. Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person{\textquoteright}s official duties. Publisher Copyright: {\textcopyright} 2016 Nature America, Inc. All rights reserved.",
year = "2016",
month = jun,
day = "1",
doi = "10.1038/nm.4110",
language = "English (US)",
volume = "22",
pages = "614--623",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "6",
}
