Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity

被引：114

作者：

Flatz, Lukas ^{[1
,2
,3
]}

Hegazy, Ahmed N. ^{[2
,4
,5
]}

Bergthaler, Andreas ^{[1
,2
,6
]}

Verschoor, Admar ^{[2
,7
]}

Claus, Christina ^{[8
]}

Fernandez, Marylise ^{[1
,9
]}

Gattinoni, Luca ^{[10
]}

Johnson, Susan ^{[1
,9
]}

Kreppel, Florian ^{[11
]}

Kochanek, Stefan ^{[11
]}

van den Broek, Maries ^{[2
,12
]}

Radbruch, Andreas ^{[4
,5
]}

Levy, Frederic ^{[13
]}

Lambert, Paul-Henri ^{[9
]}

Siegrist, Claire-Anne ^{[1
,9
,14
]}

Restifo, Nicholas P. ^{[10
]}

Loehning, Max ^{[2
,4
,5
]}

Ochsenbein, Adrian F. ^{[8
]}

Nabel, Gary J. ^{[3
]}

Pinschewer, Daniel D. ^{[1
,2
,9
]}

机构：

[1] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland

[2] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland

[3] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[4] Charite, Dept Rheumatol & Clin Immunol, D-13353 Berlin, Germany

[5] Deutsch Rheuma Forschungszentrum, Berlin, Germany

[6] Inst Syst Biol, Seattle, WA USA

[7] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany

[8] Univ Bern, Dept Clin Res, Bern, Switzerland

[9] Univ Geneva, World Hlth Org Collaborating Ctr Neonatal Vaccino, Geneva, Switzerland

[10] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[11] Univ Ulm, Div Gene Therapy, Ulm, Germany

[12] Univ Zurich Hosp, CH-8091 Zurich, Switzerland

[13] Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland

[14] Univ Geneva, Dept Pediat, Geneva, Switzerland

来源：

NATURE MEDICINE | 2010年 / 16卷 / 03期

基金：

瑞士国家科学基金会;

关键词：

DENDRITIC CELLS; LISTERIA-MONOCYTOGENES; CYTOLYTIC ACTIVITY; ANTIBODIES; MICE; RESPONSES; ADENOVIRUS; IMMUNIZATION; PREVALENCE; PROTECTION;

D O I：

10.1038/nm.2104

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Lymphocytic choriomeningitis virus (LCMV) exhibits natural tropism for dendritic cells and represents the prototypic infection that elicits protective CD8(+) T cell (cytotoxic T lymphocyte (CTL)) immunity. Here we have harnessed the immunobiology of this arenavirus for vaccine delivery. By using producer cells constitutively synthesizing the viral glycoprotein (GP), it was possible to replace the gene encoding LCMV GP with vaccine antigens to create replication-defective vaccine vectors. These rLCMV vaccines elicited CTL responses that were equivalent to or greater than those elicited by recombinant adenovirus 5 or recombinant vaccinia virus in their magnitude and cytokine profiles, and they exhibited more effective protection in several models. In contrast to recombinant adenovirus 5, rLCMV failed to elicit vector-specific antibody immunity, which facilitated re-administration of the same vector for booster vaccination. In addition, rLCMV elicited T helper type 1 CD4(+) T cell responses and protective neutralizing antibodies to vaccine antigens. These features, together with low seroprevalence in humans, suggest that rLCMV may show utility as a vaccine platform against infectious diseases and cancer.

引用

页码：339 / U142

页数：8

共 41 条

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