Clinical Assessment of a Recombinant Simian Adenovirus ChAd63: A Potent New Vaccine Vector

被引：172

作者：

O'Hara, Geraldine A. ^{[1
,2
]}

Duncan, Christopher J. A. ^{[1
,2
]}

Ewer, Katie J. ^{[1
,2
]}

Collins, Katharine A. ^{[1
,2
]}

Elias, Sean C. ^{[1
,2
]}

Halstead, Fenella D. ^{[1
,2
]}

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

Edwards, Nick J. ^{[1
,2
]}

Reyes-Sandoval, Arturo ^{[1
,2
]}

Bird, Prudence ^{[3
]}

Rowland, Rosalind ^{[1
,2
]}

Sheehy, Susanne H. ^{[1
,2
]}

Poulton, Ian D. ^{[1
,2
]}

Hutchings, Claire ^{[1
,2
]}

Todryk, Stephen ^{[1
,2
]}

Andrews, Laura ^{[1
,2
]}

Folgori, Antonella ^{[1
,2
]}

Berrie, Eleanor ^{[3
]}

Moyle, Sarah ^{[3
]}

Nicosia, Alfredo ^{[4
,5
]}

Colloca, Stefano ^{[4
]}

Cortese, Riccardo ^{[4
,5
]}

Siani, Loredana ^{[4
]}

Lawrie, Alison M. ^{[1
,2
]}

Gilbert, Sarah C. ^{[1
,2
]}

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

机构：

[1] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Headington, England

[2] Univ Oxford, Jenner Inst Labs, Headington, England

[3] Univ Oxford, Churchill Hosp, Nuffield Dept Clin Med, Clin BioMfg Facil, Headington, England

[4] Okairos AG, Rome, Italy

[5] CEINGE, Naples, Italy

来源：

JOURNAL OF INFECTIOUS DISEASES | 2012年 / 205卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

PRIME-BOOST IMMUNIZATION; T-CELLS; CIRCUMSPOROZOITE PROTEIN; MALARIA; PROTECTION; EFFICACY; CHALLENGES; CHILDREN; EPITOPE; FP9;

D O I：

10.1093/infdis/jir850

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. Vaccine development in human Plasmodium falciparum malaria has been hampered by the exceptionally high levels of CD8(+) T cells required for efficacy. Use of potently immunogenic human adenoviruses as vaccine vectors could overcome this problem, but these are limited by preexisting immunity to human adenoviruses. Methods. From 2007 to 2010, we undertook a phase I dose and route finding study of a new malaria vaccine, a replication-incompetent chimpanzee adenovirus 63 (ChAd63) encoding the preerythrocytic insert multiple epitope thrombospondin-related adhesion protein (ME-TRAP; n = 54 vaccinees) administered alone (n = 28) or with a modified vaccinia virus Ankara (MVA) ME-TRAP booster immunization 8 weeks later (n = 26). We observed an excellent safety profile. High levels of TRAP antigen-specific CD8(+) and CD4(+) T cells, as detected by interferon gamma enzyme-linked immunospot assay and flow cytometry, were induced by intramuscular ChAd63 ME-TRAP immunization at doses of 5 x 10(10) viral particles and above. Subsequent administration of MVA ME-TRAP boosted responses to exceptionally high levels, and responses were maintained for up to 30 months postvaccination. Conclusions. The ChAd63 chimpanzee adenovirus vector appears safe and highly immunogenic, providing a viable alternative to human adenoviruses as vaccine vectors for human use.

引用

页码：772 / 781

页数：10

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