经皮免疫接种减毒李斯特菌疫苗株和霍乱毒素佐剂对健康志愿者的影响。
Transcutaneous immunization of healthy volunteers with an attenuated Listeria monocytogenes vaccine strain and cholera toxin adjuvant.
机构信息
Infectious Diseases Division, Massachusetts General Hospital, Boston, MA 02114, USA.
出版信息
Vaccine. 2013 Jul 11;31(32):3257-61. doi: 10.1016/j.vaccine.2013.05.028. Epub 2013 May 22.
Abstract
BACKGROUND
Attenuated Listeria monocytogenes vaccine strains have been administered intravenously (Le et al., Maciag et al.) and orally (Angelakopoulos et al., Johnson et al.) to humans. Here, one was given transcutaneously with cholera toxin adjuvant.
METHODS
Eight healthy volunteers were studied (5 active, 3 placebo). Safety was assessed by physical exam and labs. Systemic immunological responses were measured by ELISA and IFN-gamma ELISpot.
RESULTS
4/5 active volunteers had cellular responses to listerial antigens. 5/5 active volunteers showed humoral responses to cholera toxin.
CONCLUSIONS
An attenuated L. monocytogenes vector was safely administered transcutaneously. Topical administration appeared at least as immunogenic as previously studied oral delivery.
摘要
背景
减毒李斯特菌疫苗株已通过静脉内（Le 等人，Maciag 等人）和口服（Angelakopoulos 等人，Johnson 等人）途径施用于人类。在这里，用霍乱毒素佐剂经皮给予了一种疫苗。
方法
对 8 名健康志愿者进行了研究（5 名活性，3 名安慰剂）。通过体检和实验室检查评估安全性。通过 ELISA 和 IFN-γ ELISpot 测量系统免疫反应。
结果
4/5 名活性志愿者对李斯特菌抗原产生了细胞反应。5/5 名活性志愿者对霍乱毒素表现出体液反应。
结论
经皮安全给予减毒李斯特菌载体。局部给药的免疫原性至少与先前研究的口服给药相当。
相似文献
1
Transcutaneous immunization of healthy volunteers with an attenuated Listeria monocytogenes vaccine strain and cholera toxin adjuvant.经皮免疫接种减毒李斯特菌疫苗株和霍乱毒素佐剂对健康志愿者的影响。
Vaccine. 2013 Jul 11;31(32):3257-61. doi: 10.1016/j.vaccine.2013.05.028. Epub 2013 May 22.
2
Transcutaneous immunization with bacterial ADP-ribosylating exotoxins as antigens and adjuvants.以细菌ADP - 核糖基化外毒素作为抗原和佐剂进行经皮免疫。
Infect Immun. 1999 Mar;67(3):1100-6. doi: 10.1128/IAI.67.3.1100-1106.1999.
3
Selected prfA* mutations in recombinant attenuated Listeria monocytogenes strains augment expression of foreign immunogens and enhance vaccine-elicited humoral and cellular immune responses.重组减毒单核细胞增生李斯特菌菌株中选定的prfA*突变增强了外源免疫原的表达，并增强了疫苗引发的体液免疫和细胞免疫反应。
Infect Immun. 2008 Aug;76(8):3439-50. doi: 10.1128/IAI.00245-08. Epub 2008 May 12.
4
Attenuated Listeria monocytogenes vaccine vectors expressing influenza A nucleoprotein: preclinical evaluation and oral inoculation of volunteers.表达甲型流感核蛋白的减毒李斯特菌疫苗载体：临床前评估和志愿者口服接种。
Microbiol Immunol. 2011 May;55(5):304-17. doi: 10.1111/j.1348-0421.2011.00322.x.
5
Impact of preexisting vector-specific immunity on vaccine potency: characterization of listeria monocytogenes-specific humoral and cellular immunity in humans and modeling studies using recombinant vaccines in mice.预先存在的载体特异性免疫对疫苗效力的影响：人类单核细胞增生李斯特菌特异性体液免疫和细胞免疫的特征以及在小鼠中使用重组疫苗的模型研究。
Infect Immun. 2009 Sep;77(9):3958-68. doi: 10.1128/IAI.01274-08. Epub 2009 Jun 15.
6
Sublingual Adjuvant Delivery by a Live Attenuated Vibrio cholerae-Based Antigen Presentation Platform.基于减毒霍乱弧菌的抗原呈递平台的舌下佐剂传递。
mSphere. 2018 Jun 6;3(3). doi: 10.1128/mSphere.00245-18. Print 2018 Jun 27.
7
Effect on systemic antibody concentrations of topical application of choleratoxin to skin of sheep.将霍乱毒素局部应用于绵羊皮肤对全身抗体浓度的影响。
Aust Vet J. 2000 Feb;78(2):121-3. doi: 10.1111/j.1751-0813.2000.tb10540.x.
8
Intranasal vaccination with the recombinant Listeria monocytogenes ΔactA prfA* mutant elicits robust systemic and pulmonary cellular responses and secretory mucosal IgA.用重组单核细胞增生李斯特菌ΔactA prfA*突变体进行鼻内接种可引发强烈的全身和肺部细胞反应以及分泌性黏膜IgA。
Clin Vaccine Immunol. 2011 Apr;18(4):640-6. doi: 10.1128/CVI.00254-10. Epub 2011 Jan 26.
9
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.成人志愿者中缺失actA/plcB的减毒单核细胞增生李斯特菌菌株的安全性及脱落情况：口服接种的剂量递增研究
Infect Immun. 2002 Jul;70(7):3592-601. doi: 10.1128/IAI.70.7.3592-3601.2002.
10
Comparison of mucosal and systemic humoral immune responses after transcutaneous and oral immunization strategies.经皮免疫和口服免疫策略后黏膜和全身体液免疫反应的比较。
Vaccine. 2002 Jun 21;20(21-22):2720-6. doi: 10.1016/s0264-410x(02)00208-6.
引用本文的文献
1
Transdermal Drug Delivery Systems: Methods for Enhancing Skin Permeability and Their Evaluation.经皮给药系统：增强皮肤渗透性的方法及其评价
Pharmaceutics. 2025 Jul 20;17(7):936. doi: 10.3390/pharmaceutics17070936.
2
Vaccine Strategies Against RNA Viruses: Current Advances and Future Directions.针对RNA病毒的疫苗策略：当前进展与未来方向
Vaccines (Basel). 2024 Nov 28;12(12):1345. doi: 10.3390/vaccines12121345.
3
Intracellular delivery of biologic therapeutics by bacterial secretion systems.通过细菌分泌系统进行生物治疗药物的细胞内递送。
Expert Rev Mol Med. 2017 Apr 6;19:e6. doi: 10.1017/erm.2017.7.
4
Determination of Depth-Dependent Intradermal Immunogenicity of Adjuvanted Inactivated Polio Vaccine Delivered by Microinjections via Hollow Microneedles.通过中空微针进行微量注射递送的佐剂灭活脊髓灰质炎疫苗的深度依赖性皮内免疫原性的测定。
Pharm Res. 2016 Sep;33(9):2269-79. doi: 10.1007/s11095-016-1965-6. Epub 2016 Jun 17.
5
Enhancing vaccine effectiveness with delivery technology.通过递送技术提高疫苗效力。
Curr Opin Biotechnol. 2016 Dec;42:24-29. doi: 10.1016/j.copbio.2016.02.022. Epub 2016 Mar 6.
6
Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery.活减细菌性载体：疫苗和治疗剂传递工具。
Vaccines (Basel). 2015 Nov 10;3(4):940-72. doi: 10.3390/vaccines3040940.
7
The ethics of biosafety considerations in gain-of-function research resulting in the creation of potential pandemic pathogens.功能获得性研究中生物安全考量的伦理问题，该研究导致了潜在大流行病原体的产生。
J Med Ethics. 2015 Nov;41(11):901-8. doi: 10.1136/medethics-2014-102619. Epub 2015 Aug 28.
8
Immunogenicity of a West Nile virus DIII-cholera toxin A2/B chimera after intranasal delivery.西尼罗河病毒DIII-霍乱毒素A2/B嵌合体经鼻内递送后的免疫原性。
Toxins (Basel). 2014 Apr 22;6(4):1397-418. doi: 10.3390/toxins6041397.
本文引用的文献
1
Clinical development of Listeria monocytogenes-based immunotherapies.李斯特菌属基于免疫疗法的临床发展。
Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.
2
Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity.皮肤感染产生非迁移性记忆 CD8+T（RM）细胞，提供全身皮肤免疫。
Nature. 2012 Feb 29;483(7388):227-31. doi: 10.1038/nature10851.
3
A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction.用于晚期癌症的减毒李斯特菌疫苗（ANZ-100）和表达间皮素的减毒李斯特菌疫苗（CRS-207）：安全性和免疫原性的 I 期研究。
Clin Cancer Res. 2012 Feb 1;18(3):858-68. doi: 10.1158/1078-0432.CCR-11-2121. Epub 2011 Dec 6.
4
Intradermal fractional dose inactivated polio vaccine: a review of the literature.皮内分剂量灭活脊髓灰质炎疫苗：文献复习。
Vaccine. 2012 Jan 5;30(2):121-5. doi: 10.1016/j.vaccine.2011.11.018. Epub 2011 Nov 17.
5
Attenuated Listeria monocytogenes vaccine vectors expressing influenza A nucleoprotein: preclinical evaluation and oral inoculation of volunteers.表达甲型流感核蛋白的减毒李斯特菌疫苗载体：临床前评估和志愿者口服接种。
Microbiol Immunol. 2011 May;55(5):304-17. doi: 10.1111/j.1348-0421.2011.00322.x.
6
Skin-resident T cells: the ups and downs of on site immunity.皮肤驻留 T 细胞：局部免疫的起伏。
J Invest Dermatol. 2010 Feb;130(2):362-70. doi: 10.1038/jid.2009.247. Epub 2009 Aug 13.
7
The first clinical use of a live-attenuated Listeria monocytogenes vaccine: a Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix.减毒活单核细胞增生李斯特菌疫苗的首次临床应用：Lm-LLO-E7在晚期宫颈癌患者中的I期安全性研究。
Vaccine. 2009 Jun 19;27(30):3975-83. doi: 10.1016/j.vaccine.2009.04.041. Epub 2009 May 3.
8
Improved immune responses to influenza vaccination in the elderly using an immunostimulant patch.使用免疫刺激贴片改善老年人对流感疫苗的免疫反应。
Vaccine. 2005 Jan 4;23(7):946-50. doi: 10.1016/j.vaccine.2004.06.036.
9
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.成人志愿者中缺失actA/plcB的减毒单核细胞增生李斯特菌菌株的安全性及脱落情况：口服接种的剂量递增研究
Infect Immun. 2002 Jul;70(7):3592-601. doi: 10.1128/IAI.70.7.3592-3601.2002.
10
Safety and immunogenicity of a prototype enterotoxigenic Escherichia coli vaccine administered transcutaneously.经皮接种的原型产肠毒素大肠杆菌疫苗的安全性和免疫原性。
Infect Immun. 2002 Apr;70(4):1874-80. doi: 10.1128/IAI.70.4.1874-1880.2002.
Zotero 插件