Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation

被引：232

作者：

Ewer, Katie J. ^{[1
]}

O'Hara, Geraldine A. ^{[2
]}

Duncan, Christopher J. A. ^{[2
]}

Collins, Katharine A. ^{[1
]}

Sheehy, Susanne H. ^{[2
]}

Reyes-Sandoval, Arturo ^{[1
]}

Goodman, Anna L. ^{[1
,2
]}

Edwards, Nick J. ^{[1
]}

Elias, Sean C. ^{[1
]}

Halstead, Fenella D. ^{[1
]}

Longley, Rhea J. ^{[1
]}

Rowland, Rosalind ^{[2
]}

Poulton, Ian D. ^{[2
]}

Draper, Simon J. ^{[1
]}

Blagborough, Andrew M. ^{[3
]}

Berrie, Eleanor ^{[4
]}

Moyle, Sarah ^{[4
]}

Williams, Nicola ^{[5
]}

Siani, Loredana ^{[6
]}

Folgori, Antonella ^{[6
]}

Colloca, Stefano ^{[6
]}

Sinden, Robert E. ^{[1
,3
]}

Lawrie, Alison M. ^{[2
]}

Cortese, Riccardo ^{[6
]}

Gilbert, Sarah C. ^{[1
]}

Nicosia, Alfredo ^{[6
,7
,8
]}

Hill, Adrian V. S. ^{[1
,2
]}

机构：

[1] Univ Oxford, Jenner Inst Labs, Oxford OX3 7DQ, England

[2] Univ Oxford, Churchill Hosp, Ctr Clin Vaccinol & Trop Med, Oxford OX3 7LJ, England

[3] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London SW7 2AZ, England

[4] Univ Oxford, Churchill Hosp, Clin Biomfg Facil, Oxford OX3 7JT, England

[5] Ctr Stat Med, Oxford OX2 6UD, England

[6] Okairos, I-00144 Rome, Italy

[7] CEINGE, I-80145 Naples, Italy

[8] Univ Naples Federico II, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

基金：

英国惠康基金;

关键词：

VACCINIA VIRUS ANKARA; POLYMERASE-CHAIN-REACTION; PRIME-BOOST IMMUNIZATION; PHASE 2A TRIAL; NAIVE ADULTS; MEDIATED PROTECTION; NONHUMAN-PRIMATES; INFLUENZA-VIRUS; RHESUS-MONKEYS; DNA VACCINES;

D O I：

10.1038/ncomms3836

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：

07 ; 0710 ; 09 ;

摘要：

Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-gamma-producing CD8(+) T cells, but not antibodies, correlates with sterile protection and delay in time to patency (P-corrected = 0.005). Vaccine-induced CD8(+) T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.

引用

页数：10

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