Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8+ T Cell Immunity

被引：394

作者：

Epstein, J. E. ^{[2
]}

Tewari, K. ^{[1
]}

Lyke, K. E. ^{[3
]}

Sim, B. K. L. ^{[4
,5
]}

Billingsley, P. F. ^{[4
]}

Laurens, M. B. ^{[3
,6
]}

Gunasekera, A. ^{[4
]}

Chakravarty, S. ^{[4
]}

James, E. R. ^{[4
]}

Sedegah, M. ^{[2
]}

Richman, A. ^{[4
]}

Velmurugan, S. ^{[4
]}

Reyes, S. ^{[2
]}

Li, M. ^{[5
]}

Tucker, K. ^{[7
]}

Ahumada, A. ^{[4
,5
]}

Ruben, A. J. ^{[4
]}

Li, T. ^{[4
]}

Stafford, R. ^{[4
,5
]}

Eappen, A. G. ^{[4
]}

Tamminga, C. ^{[2
]}

Bennett, J. W. ^{[8
]}

Ockenhouse, C. F. ^{[8
]}

Murphy, J. R. ^{[8
]}

Komisar, J. ^{[8
]}

Thomas, N. ^{[2
]}

Loyevsky, M. ^{[4
]}

Birkett, A. ^{[9
]}

Plowe, C. V. ^{[3
,6
]}

Loucq, C. ^{[9
]}

Edelman, R. ^{[3
]}

Richie, T. L. ^{[2
]}

Seder, R. A. ^{[1
]}

Hoffman, S. L. ^{[4
,5
]}

机构：

[1] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA

[2] USN, Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD 20910 USA

[3] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA

[4] Sanaria Inc, Rockville, MD 20850 USA

[5] Prot Potential LLC, Rockville, MD 20850 USA

[6] Howard Hughes Med Inst, Baltimore, MD 21201 USA

[7] Stat Collaborat Inc, Washington, DC 20036 USA

[8] Walter Reed Army Inst Res, US Mil Malaria Vaccine Program, Silver Spring, MD 20910 USA

[9] PATH Malaria Vaccine Initiat, Bethesda, MD 20814 USA

来源：

SCIENCE | 2011年 / 334卷 / 6055期

关键词：

SPOROZOITE SURFACE PROTEIN-2; PLASMODIUM-FALCIPARUM SPOROZOITES; CIRCUMSPOROZOITE PROTEIN; INFECTED HEPATOCYTES; PREERYTHROCYTIC STAGES; GAMMA-INTERFERON; IMMUNIZATION; RESPONSES; HUMANS; MICE;

D O I：

10.1126/science.1211548

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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-gamma (IFN-gamma). We report that purified irradiated Pf SPZ 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 Pf SPZ-specific CD8(+), IFN-gamma-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.

引用

页码：475 / 480

页数：6

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