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

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

doi:10.1038/nm.4110

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

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

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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 â 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.

Original language	English (US)
Pages (from-to)	614-623
Number of pages	10
Journal	Nature medicine
Volume	22
Issue number	6
DOIs	https://doi.org/10.1038/nm.4110
State	Published - Jun 1 2016
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Ishizuka, A. S., Lyke, K. E., DeZure, A., Berry, A. A., Richie, T. L., Mendoza, F. H., Enama, M. E., Gordon, I. J., Chang, L. J., Sarwar, U. N., Zephir, K. L., Holman, L. A., James, E. R., Billingsley, P. F., Gunasekera, A., Chakravarty, S., Manoj, A., Li, M., Ruben, A. J., ... Seder, R. A. (2016). Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nature medicine, 22(6), 614-623. https://doi.org/10.1038/nm.4110

Ishizuka, AS, Lyke, KE, DeZure, A, Berry, AA, Richie, TL, Mendoza, FH, Enama, ME, Gordon, IJ, Chang, LJ, Sarwar, UN, Zephir, KL, Holman, LA, James, ER, Billingsley, PF, Gunasekera, A, Chakravarty, S, Manoj, A, Li, M, Ruben, AJ, Li, T, Eappen, AG, Stafford, RE, Natasha, KC, Murshedkar, T, DeCederfelt, H, Plummer, SH, Hendel, CS, Novik, L, Costner, PJM, Saunders, JG, Laurens, MB, Plowe, CV, Flynn, B, Whalen, WR, Todd, JP, Noor, J, Rao, S, Sierra-Davidson, K, Lynn, GM, Epstein, JE, Kemp, MA, Fahle, GA, Mikolajczak, SA, Fishbaugher, M, Sack, BK, Kappe, SHI, Davidson, SA, Garver, LS, Björkström, NK, Nason, MC, Graham, BS, Roederer, M, Kim Lee Sim, B, Hoffman, SL, Ledgerwood, JE & Seder, RA 2016, 'Protection against malaria at 1 year and immune correlates following PfSPZ vaccination', Nature medicine, vol. 22, no. 6, pp. 614-623. https://doi.org/10.1038/nm.4110

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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.}",

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doi = "10.1038/nm.4110",

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T1 - Protection against malaria at 1 year and immune correlates following PfSPZ vaccination

AU - Ishizuka, Andrew S.

AU - Lyke, Kirsten E.

AU - DeZure, Adam

AU - Berry, Andrea A.

AU - Richie, Thomas L.

AU - Mendoza, Floreliz H.

AU - Enama, Mary E.

AU - Gordon, Ingelise J.

AU - Chang, Lee Jah

AU - Sarwar, Uzma N.

AU - Zephir, Kathryn L.

AU - Holman, Lasonji A.

AU - James, Eric R.

AU - Billingsley, Peter F.

AU - Gunasekera, Anusha

AU - Chakravarty, Sumana

AU - Manoj, Anita

AU - Li, Minglin

AU - Ruben, Adam J.

AU - Li, Tao

AU - Eappen, Abraham G.

AU - Stafford, Richard E.

AU - Natasha, K. C.

AU - Murshedkar, Tooba

AU - DeCederfelt, Hope

AU - Plummer, Sarah H.

AU - Hendel, Cynthia S.

AU - Novik, Laura

AU - Costner, Pamela J.M.

AU - Saunders, Jamie G.

AU - Laurens, Matthew B.

AU - Plowe, Christopher V.

AU - Flynn, Barbara

AU - Whalen, William R.

AU - Todd, J. P.

AU - Noor, Jay

AU - Rao, Srinivas

AU - Sierra-Davidson, Kailan

AU - Lynn, Geoffrey M.

AU - Epstein, Judith E.

AU - Kemp, Margaret A.

AU - Fahle, Gary A.

AU - Mikolajczak, Sebastian A.

AU - Fishbaugher, Matthew

AU - Sack, Brandon K.

AU - Kappe, Stefan H.I.

AU - Davidson, Silas A.

AU - Garver, Lindsey S.

AU - Björkström, Niklas K.

AU - Nason, Martha C.

AU - Graham, Barney S.

AU - Roederer, Mario

AU - Kim Lee Sim, B.

AU - Hoffman, Stephen L.

AU - Ledgerwood, Julie E.

AU - Seder, Robert A.

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

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