Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine

Robert A. Seder; Lee Jah Chang; Mary E. Enama; Kathryn L. Zephir; Uzma N. Sarwar; Ingelise J. Gordon; La Sonji A. Holman; Eric R. James; Peter F. Billingsley; Anusha Gunasekera; Adam Richman; Sumana Chakravarty; Anita Manoj; Soundarapandian Velmurugan; Ming Lin Li; Adam J. Ruben; Tao Li; Abraham G. Eappen; Richard E. Stafford; Sarah H. Plummer; Cynthia S. Hendel; Laura Novik; Pamela J.M. Costner; Floreliz H. Mendoza; Jamie G. Saunders; Martha C. Nason; Jason H. Richardson; Jittawadee Murphy; Silas A. Davidson; Thomas L. Richie; Martha Sedegah; Awalludin Sutamihardja; Gary A. Fahle; Kirsten E. Lyke; Matthew B. Laurens; Mario Roederer; Kavita Tewari; Judith E. Epstein; B. Kim Lee Sim; Julie E. Ledgerwood; Barney S. Graham; Stephen L. Hoffman

doi:10.1126/science.1241800

Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine

Robert A. Seder, Lee Jah Chang, Mary E. Enama, Kathryn L. Zephir, Uzma N. Sarwar, Ingelise J. Gordon, La Sonji A. Holman, Eric R. James, Peter F. Billingsley, Anusha Gunasekera, Adam Richman, Sumana Chakravarty, Anita Manoj, Soundarapandian Velmurugan, Ming Lin Li, Adam J. Ruben, Tao Li, Abraham G. Eappen, Richard E. Stafford, Sarah H. PlummerCynthia S. Hendel, Laura Novik, Pamela J.M. Costner, Floreliz H. Mendoza, Jamie G. Saunders, Martha C. Nason, Jason H. Richardson, Jittawadee Murphy, Silas A. Davidson, Thomas L. Richie, Martha Sedegah, Awalludin Sutamihardja, Gary A. Fahle, Kirsten E. Lyke, Matthew B. Laurens, Mario Roederer, Kavita Tewari, Judith E. Epstein, B. Kim Lee Sim, Julie E. Ledgerwood, Barney S. Graham, Stephen L. Hoffman

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Abstract

Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine - composed of attenuated, aseptic, purified, cryopreserved PfSPZ - was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 10⁵ PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

Original language	English (US)
Pages (from-to)	1359-1365
Number of pages	7
Journal	Science
Volume	341
Issue number	6152
DOIs	https://doi.org/10.1126/science.1241800
State	Published - 2013
Externally published	Yes

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Seder, R. A., Chang, L. J., Enama, M. E., Zephir, K. L., Sarwar, U. N., Gordon, I. J., Holman, L. S. A., James, E. R., Billingsley, P. F., Gunasekera, A., Richman, A., Chakravarty, S., Manoj, A., Velmurugan, S., Li, M. L., Ruben, A. J., Li, T., Eappen, A. G., Stafford, R. E., ... Hoffman, S. L. (2013). Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science, 341(6152), 1359-1365. https://doi.org/10.1126/science.1241800

Seder, RA, Chang, LJ, Enama, ME, Zephir, KL, Sarwar, UN, Gordon, IJ, Holman, LSA, James, ER, Billingsley, PF, Gunasekera, A, Richman, A, Chakravarty, S, Manoj, A, Velmurugan, S, Li, ML, Ruben, AJ, Li, T, Eappen, AG, Stafford, RE, Plummer, SH, Hendel, CS, Novik, L, Costner, PJM, Mendoza, FH, Saunders, JG, Nason, MC, Richardson, JH, Murphy, J, Davidson, SA, Richie, TL, Sedegah, M, Sutamihardja, A, Fahle, GA, Lyke, KE, Laurens, MB, Roederer, M, Tewari, K, Epstein, JE, Sim, BKL, Ledgerwood, JE, Graham, BS & Hoffman, SL 2013, 'Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine', Science, vol. 341, no. 6152, pp. 1359-1365. https://doi.org/10.1126/science.1241800

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title = "Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine",

abstract = "Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine - composed of attenuated, aseptic, purified, cryopreserved PfSPZ - was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.",

author = "Seder, {Robert A.} and Chang, {Lee Jah} and Enama, {Mary E.} and Zephir, {Kathryn L.} and Sarwar, {Uzma N.} and Gordon, {Ingelise J.} and Holman, {La Sonji A.} and James, {Eric R.} and Billingsley, {Peter F.} and Anusha Gunasekera and Adam Richman and Sumana Chakravarty and Anita Manoj and Soundarapandian Velmurugan and Li, {Ming Lin} and Ruben, {Adam J.} and Tao Li and Eappen, {Abraham G.} and Stafford, {Richard E.} and Plummer, {Sarah H.} and Hendel, {Cynthia S.} and Laura Novik and Costner, {Pamela J.M.} and Mendoza, {Floreliz H.} and Saunders, {Jamie G.} and Nason, {Martha C.} and Richardson, {Jason H.} and Jittawadee Murphy and Davidson, {Silas A.} and Richie, {Thomas L.} and Martha Sedegah and Awalludin Sutamihardja and Fahle, {Gary A.} and Lyke, {Kirsten E.} and Laurens, {Matthew B.} and Mario Roederer and Kavita Tewari and Epstein, {Judith E.} and Sim, {B. Kim Lee} and Ledgerwood, {Julie E.} and Graham, {Barney S.} and Hoffman, {Stephen L.}",

year = "2013",

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T1 - Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine

AU - Seder, Robert A.

AU - Chang, Lee Jah

AU - Enama, Mary E.

AU - Zephir, Kathryn L.

AU - Sarwar, Uzma N.

AU - Gordon, Ingelise J.

AU - Holman, La Sonji A.

AU - James, Eric R.

AU - Billingsley, Peter F.

AU - Gunasekera, Anusha

AU - Richman, Adam

AU - Chakravarty, Sumana

AU - Manoj, Anita

AU - Velmurugan, Soundarapandian

AU - Li, Ming Lin

AU - Ruben, Adam J.

AU - Li, Tao

AU - Eappen, Abraham G.

AU - Stafford, Richard E.

AU - Plummer, Sarah H.

AU - Hendel, Cynthia S.

AU - Novik, Laura

AU - Costner, Pamela J.M.

AU - Mendoza, Floreliz H.

AU - Saunders, Jamie G.

AU - Nason, Martha C.

AU - Richardson, Jason H.

AU - Murphy, Jittawadee

AU - Davidson, Silas A.

AU - Richie, Thomas L.

AU - Sedegah, Martha

AU - Sutamihardja, Awalludin

AU - Fahle, Gary A.

AU - Lyke, Kirsten E.

AU - Laurens, Matthew B.

AU - Roederer, Mario

AU - Tewari, Kavita

AU - Epstein, Judith E.

AU - Sim, B. Kim Lee

AU - Ledgerwood, Julie E.

AU - Graham, Barney S.

AU - Hoffman, Stephen L.

PY - 2013

Y1 - 2013

N2 - Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine - composed of attenuated, aseptic, purified, cryopreserved PfSPZ - was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

AB - Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine - composed of attenuated, aseptic, purified, cryopreserved PfSPZ - was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

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DO - 10.1126/science.1241800

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SP - 1359

EP - 1365

JO - Science

JF - Science

IS - 6152

ER -

Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine

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