Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity

J. E. Epstein; K. Tewari; K. E. Lyke; B. K.L. Sim; P. F. Billingsley; M. B. Laurens; A. Gunasekera; S. Chakravarty; E. R. James; M. Sedegah; A. Richman; S. Velmurugan; S. Reyes; M. Li; K. Tucker; A. Ahumada; A. J. Ruben; T. Li; R. Stafford; A. G. Eappen; C. Tamminga; J. W. Bennett; C. F. Ockenhouse; J. R. Murphy; J. Komisar; N. Thomas; M. Loyevsky; A. Birkett; C. V. Plowe; C. Loucq; R. Edelman; T. L. Richie; R. A. Seder; S. L. Hoffman

doi:10.1126/science.1211548

Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity

J. E. Epstein, K. Tewari, K. E. Lyke, B. K.L. Sim, P. F. Billingsley, M. B. Laurens, A. Gunasekera, S. Chakravarty, E. R. James, M. Sedegah, A. Richman, S. Velmurugan, S. Reyes, M. Li, K. Tucker, A. Ahumada, A. J. Ruben, T. Li, R. Stafford, A. G. EappenC. Tamminga, J. W. Bennett, C. F. Ockenhouse, J. R. Murphy, J. Komisar, N. Thomas, M. Loyevsky, A. Birkett, C. V. Plowe, C. Loucq, R. Edelman, T. L. Richie, R. A. Seder^*, S. L. Hoffman

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

435 Scopus citations

Abstract

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (Pf SPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8 ⁺ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8⁺, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Original language	English
Pages (from-to)	475-480
Number of pages	6
Journal	Science
Volume	334
Issue number	6055
DOIs	https://doi.org/10.1126/science.1211548
State	Published - 28 Oct 2011
Externally published	Yes

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Epstein, J. E., Tewari, K., Lyke, K. E., Sim, B. K. L., Billingsley, P. F., Laurens, M. B., Gunasekera, A., Chakravarty, S., James, E. R., Sedegah, M., Richman, A., Velmurugan, S., Reyes, S., Li, M., Tucker, K., Ahumada, A., Ruben, A. J., Li, T., Stafford, R., ... Hoffman, S. L. (2011). Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity. Science, 334(6055), 475-480. https://doi.org/10.1126/science.1211548

@article{056ee213e9c74f1796e778003ce4df9b,

title = "Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity",

abstract = "Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (Pf SPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8 + T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8+, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.",

author = "Epstein, {J. E.} and K. Tewari and Lyke, {K. E.} and Sim, {B. K.L.} and Billingsley, {P. F.} and Laurens, {M. B.} and A. Gunasekera and S. Chakravarty and James, {E. R.} and M. Sedegah and A. Richman and S. Velmurugan and S. Reyes and M. Li and K. Tucker and A. Ahumada and Ruben, {A. J.} and T. Li and R. Stafford and Eappen, {A. G.} and C. Tamminga and Bennett, {J. W.} and Ockenhouse, {C. F.} and Murphy, {J. R.} and J. Komisar and N. Thomas and M. Loyevsky and A. Birkett and Plowe, {C. V.} and C. Loucq and R. Edelman and Richie, {T. L.} and Seder, {R. A.} and Hoffman, {S. L.}",

year = "2011",

month = oct,

day = "28",

doi = "10.1126/science.1211548",

language = "English",

volume = "334",

pages = "475--480",

journal = "Science",

issn = "0036-8075",

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Epstein, JE, Tewari, K, Lyke, KE, Sim, BKL, Billingsley, PF, Laurens, MB, Gunasekera, A, Chakravarty, S, James, ER, Sedegah, M, Richman, A, Velmurugan, S, Reyes, S, Li, M, Tucker, K, Ahumada, A, Ruben, AJ, Li, T, Stafford, R, Eappen, AG, Tamminga, C, Bennett, JW, Ockenhouse, CF, Murphy, JR, Komisar, J, Thomas, N, Loyevsky, M, Birkett, A, Plowe, CV, Loucq, C, Edelman, R, Richie, TL, Seder, RA & Hoffman, SL 2011, 'Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity', Science, vol. 334, no. 6055, pp. 475-480. https://doi.org/10.1126/science.1211548

TY - JOUR

T1 - Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity

AU - Epstein, J. E.

AU - Tewari, K.

AU - Lyke, K. E.

AU - Sim, B. K.L.

AU - Billingsley, P. F.

AU - Laurens, M. B.

AU - Gunasekera, A.

AU - Chakravarty, S.

AU - James, E. R.

AU - Sedegah, M.

AU - Richman, A.

AU - Velmurugan, S.

AU - Reyes, S.

AU - Li, M.

AU - Tucker, K.

AU - Ahumada, A.

AU - Ruben, A. J.

AU - Li, T.

AU - Stafford, R.

AU - Eappen, A. G.

AU - Tamminga, C.

AU - Bennett, J. W.

AU - Ockenhouse, C. F.

AU - Murphy, J. R.

AU - Komisar, J.

AU - Thomas, N.

AU - Loyevsky, M.

AU - Birkett, A.

AU - Plowe, C. V.

AU - Loucq, C.

AU - Edelman, R.

AU - Richie, T. L.

AU - Seder, R. A.

AU - Hoffman, S. L.

PY - 2011/10/28

Y1 - 2011/10/28

N2 - Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (Pf SPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8 + T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8+, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

AB - Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (Pf SPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8 + T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8+, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

UR - http://www.scopus.com/inward/record.url?scp=80055087402&partnerID=8YFLogxK

U2 - 10.1126/science.1211548

DO - 10.1126/science.1211548

M3 - Article

AN - SCOPUS:80055087402

SN - 0036-8075

VL - 334

SP - 475

EP - 480

JO - Science

JF - Science

IS - 6055

ER -

Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell immunity

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Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity