Fine-tuning the safety and immunogenicity of Listeria monocytogenes-based neonatal vaccine platforms

被引：7

作者：

Loeffler, Daniela I. M. ^{[1
]}

Smolen, Kinga ^{[1
]}

Aplin, Laura ^{[1
]}

Cai, Bing ^{[1
]}

Kollmann, Tobias R. ^{[1
]}

机构：

[1] Univ British Columbia, Dept Paediat, Div Infect & Immunol Dis, Child & Family Res Inst, Vancouver, BC, Canada

来源：

VACCINE | 2009年 / 27卷 / 06期

关键词：

Listeria monocytogenes; Live vaccines; Newborns; CD8(+) T-CELLS; IMMUNE-RESPONSES; VIRULENCE GENES; EARLY-LIFE; IFN-GAMMA; IN-VIVO; ANTIGEN; EXPRESSION; INDUCTION; INFECTION;

D O I：

10.1016/j.vaccine.2008.11.047

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We have developed virulence-attenuated strains of Listeria monocytogenes (Lm) that can be Used as safe yet effective vaccine carriers for neonatal vaccination. Here we compare the vaccine efficacy of Lm based vaccine carrier candidates after only a single immunization in murine neonates and adults: Lm Delta(trpS acrA) based strains that express and secrete multiple copies of the model antigen ovalbumin (OVA) either under the control of a phagosomal (P-hly) or cytosolic (P-actA)-driven listerial promoter. While both strains induced high levels of antigen-specific primary and secondary CD8 and CD4T cell responses, both neonatal and adult mice immunized with the phagosomal driven strain were significantly better protected against wildtype Lm challenge as compared to the naive control group than mice immunized with the cytosolic driven strains. Interestingly, only neonatal Mice immunized with the phagosomal driven strains generated high IgG antibody responses against OVA. Our phagosomal driven Lm-based vaccine platform presents the broadest (cellular & humoral response) and most efficient (highly protective) vaccine platform for neonatal vaccination yet described. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：919 / 927

页数：9

共 46 条

[1] Neonatal adaptive immunity comes of age [J].

Adkins, B ;

Leclerc, C ;

Marshall-Clarke, S .

NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :553-564

[2]

ADKINS B, 2005, J PEDIAT GASTROENTER, V40, P5

[3] Safety and shedding of an attenuated strain of Listeria monocytogenes with a deletion of actA/plcB in adult volunteers:: a dose escalation study of oral inoculation [J].

Angelakopoulos, H ;

Loock, K ;

Sisul, DM ;

Jensen, ER ;

Miller, JF ;

Hohmann, EL .

INFECTION AND IMMUNITY, 2002, 70 (07) :3592-3601

[4] Intracellular staining for TNF and IFN-γ detects different frequencies of antigen-specific CD8+ T cells [J].

Badovinac, VP ;

Harty, JT .

JOURNAL OF IMMUNOLOGICAL METHODS, 2000, 238 (1-2) :107-117

[5] Programmed contraction of CD8+ T cells after infection [J].

Badovinac, VP ;

Porter, BB ;

Harty, JT .

NATURE IMMUNOLOGY, 2002, 3 (07) :619-626

[6] Cytosolic entry controls CD8+-T-cell potency during bacterial infection [J].

Bahjat, Keith S. ;

Liu, Weiqun ;

Lemmens, Edward E. ;

Schoenberger, Stephen P. ;

Portnoy, Daniel A. ;

Dubensky, Thomas W., Jr. ;

Brockstedt, Dirk G. .

INFECTION AND IMMUNITY, 2006, 74 (11) :6387-6397

[7] Salmonella-mediated oral DNA vaccination using stabilized eukaryotic expression plasmids [J].

Bauer, H ;

Darji, A ;

Chakraborty, T ;

Weiss, S .

GENE THERAPY, 2005, 12 (04) :364-372

[8] Promises and challenges for the development of Listeria monocytogenes-based immunotherapies [J].

Brockstedt, Dirk G. ;

Dubensky, Thomas W., Jr. .

EXPERT REVIEW OF VACCINES, 2008, 7 (07) :1069-1084

[9] Listeria as a vaccine vector [J].

Bruhn, Kevin W. ;

Craft, Noah ;

Miller, Jeff F. .

MICROBES AND INFECTION, 2007, 9 (10) :1226-1235

[10] Cytoplasmic entry of Listeria monocytogenes enhances dendritic cell maturation and T cell differentiation and function [J].

Brzoza, KL ;

Rockel, AB ;

Hiltbold, EM .

JOURNAL OF IMMUNOLOGY, 2004, 173 (04) :2641-2651

← 1 2 3 4 5 →