浏览全部资源
扫码关注微信
不同佐剂对重组鲍曼不动杆菌PKF的免疫效果研究
Comparison of different adjuvants for immune efficacy of recombinant PKF protein of
Acinetobacter baumannii - 陆军军医大学学报 2023年45卷第9期 页码：957-963
- 作者机构：
1.154007 黑龙江 佳木斯, 佳木斯大学临床医学院
2.400038 重庆, 陆军军医大学(第三军医大学)药学与检验医学系微生物与生化药学教研室, 国家免疫生物制品工程技术研究中心
- 作者简介：
[李海波，E-mail：lihaibo@tmmu.edu.cnLI Haibo, E-mail: lihaibo@tmmu.edu.cn
[高英英，E-mail：happygaoyingying@163.comGAO Yingying, E-mail: happygaoyingying@163.com
- 基金信息：重庆市自然科学基金重点项目(cstc2020jcyj-zdxmX0027);国家自然科学基金面上项目(32270988)
DOI：10.16016/j.2097-0927.202211213
中图分类号： R378.7;R392.7收稿：2022-11-28，
修回：2023-01-21，
纸质出版：2023-05-15
- 稿件说明：
移动端阅览
张珊珊, 李郭成, 冯壤, 等. 不同佐剂对重组鲍曼不动杆菌PKF的免疫效果研究[J]. 陆军军医大学学报, 2023,45(9):957-963.
Shanshan ZHANG, Guocheng LI, Rang FENG, et al. Comparison of different adjuvants for immune efficacy of recombinant PKF protein of
Acinetobacter baumannii [J]. Journal of Army Medical University, 2023, 45(9): 957-963.张珊珊, 李郭成, 冯壤, 等. 不同佐剂对重组鲍曼不动杆菌PKF的免疫效果研究[J]. 陆军军医大学学报, 2023,45(9):957-963. DOI： 10.16016/j.2097-0927.202211213.
Shanshan ZHANG, Guocheng LI, Rang FENG, et al. Comparison of different adjuvants for immune efficacy of recombinant PKF protein of
Acinetobacter baumannii [J]. Journal of Army Medical University, 2023, 45(9): 957-963. DOI： 10.16016/j.2097-0927.202211213.
摘要
目的
2
比较不同免疫方式、不同佐剂对重组鲍曼不动杆菌PKF的免疫效果。
方法
2
构建重组质粒
经诱导表达纯化获得重组PKF
分别联合氢氧化铝、AS03肌注(intramuscular
im)免疫以及LTK63、LP1-34滴鼻(intranasally
in)免疫小鼠
共分为7组: PBS组; 肌注免疫组: PKF (im)组、PKF+Al (im)组、PKF+AS03(im)组; 滴鼻免疫组: PKF (in)组、PKF+LTK63(in)组、PKF+LP1-34(in)组。ELISA检测免疫后小鼠血清中特异性IgG以及黏膜部位sIgA的水平; 构建鲍曼不动杆菌肺部感染亚致死模型
测定攻毒后小鼠血液和肺部细菌定植量
评价疫苗保护作用。
结果
2
肌注免疫组中
AS03辅助PKF诱导最高的特异性IgG抗体水平(
P
<
0.01);滴鼻免疫组中
LTK63显著提升肺泡灌洗液中特异性sIgA水平(
P
<
0.01);攻毒后细菌定植量检测结果显示
PKF+AS03肌注组细菌定植量与单用PKF组相当
而滴鼻组中LTK63可以显著降低细菌定植量(
P
<
0.01)。
结论
2
LTK63可以辅助PKF更好地发挥对鲍曼不动杆菌肺部感染的保护作用
表明疫苗介导的黏膜免疫应答对保护感染可能更加重要。
Abstract
Objective
2
To compare the immune effects of recombinant PKF protein of
Acinetobacter baumannii
with different immune modes and different adjuvants.
Methods
2
After recombinant PKF protein was obtained by plasmid expression and purification
the protein was then combined w
ith aluminum hydroxide (Al) or with AS03 to immunize mice by intramuscular (im) injection.In another experiment
the combination of PKF and LTK63 or PKF and LP1-34 was adopted to intranasally (in) immunize mice
respectively.The total animals were thus divided into 7 groups: PBS group; PKF group (im)
PKF+Al group (im)
PKF+AS03 group (im)
PKF group (in)
PKF+LTK63 group (in)
and PKF+LP1-34 group (in).The levels of serum specific IgG and mucosal sIgA in the immunized mice were detected by ELISA.Moreover
the sublethal model of
Acinetobacter baumannii
pulmonary infection was established
and then the bacterial colonization amount in blood and lung of mice after challenge was measured to evaluate the protective immune efficacy of the recombinant vaccine.
Results
2
In the intramuscular immunization group
AS03-assisted PKF produced the highest specific IgG antibody level (
P
<
0.01)
and in the nasal immunization group
LTK63 significantly increased the level of specific sIgA in the alveolar lavage fluid (
P
<
0.01).Bacterial challenge test showed that the bacterial colonization amount was similar in the PKF+AS03(im) group and PKF (im) alone group
while the PKF+LTK63 group (in) obtained remarkably reduced bacterial colonization amount (
P
<
0.01).
Conclusion
2
LTK63 assists PKF to better protect against
Acinetobacter baumannii
pulmonary infection
suggesting that vaccine-mediated mucosal immune response may play a more important role in the infection protection.
关键词
Keywords
references
DIANCOURT L, PASSET V, NEMEC A, et al . The population structure of Acinetobacter baumannii : expanding multiresistant clones from an ancestral susceptible genetic pool[J ] . PLoS One, 2010, 5(4): e10034. DOI: 10.1371/journal.pone.0010034..
ROCA I, ESPINAL P, VILA-FARRÉS X, et al . The Acinetobacter baumannii oxymoron: commensal hospital dweller turned pan-drug-resistant menace[J ] . Front Microbiol, 2012, 3: 148. DOI: 10.3389/fmicb.2012.00148..
WONG D, NIELSEN T B, BONOMO R A, et al . Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges[J ] . Clin Microbiol Rev, 2017, 30(1): 409-447. DOI: 10.1128/CMR.00058-16..
BENTANCOR L V, ROUTRAY A, BOZKURT-GUZEL C, et al . Evaluation of the trimeric autotransporter Ata as a vaccine candidate against Acinetobacter baumannii infections[J ] . Infect Immun, 2012, 80(10): 3381-3388. DOI: 10.1128/IAI.06096-11..
LAVELLE E C, WARD R W. Publisher correction: mucosal vaccines - fortifying the frontiers[J]. Nat Rev Immunol, 2022, 22(4): 266. DOI: 10.1038/s41577-021-00599-8.
ZHANG X J, YANG T X, CAO J, et al . Mucosal immunization with purified OmpA elicited protective immunity against infections caused by multidrug-resistant Acinetobacter baumannii [J ] . Microb Pathog, 2016, 96: 20-25. DOI: 10.1016/j.micpath.2016.04.019..
GUO S J, REN S, XIE Y E. Evaluation of the protective efficacy of a fused OmpK/Omp22 protein vaccine candidate against Acinetobacter baumannii infection in mice[J ] . Biomed Environ Sci, 2018, 31(2): 155-158. DOI: 10.3967/bes2018.019.
HUANG W W, WANG S J, YAO Y F, et al . OmpW is a potential target for eliciting protective immunity against Acinetobacter baumannii infections[J ] . Vaccine, 2015, 33(36): 4479-4485. DOI: 10.1016/j.vaccine.2015.07.031..
HUANG W W, YAO Y F, WANG S J, et al . Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii [J ] . Sci Rep, 2016, 6: 20724. DOI: 10.1038/srep20724..
BOLOURCHI N, SHAHCHERAGHI F, SHIRAZI A S, et al . Immunogenic reactivity of recombinant PKF and AbOmpA proteins as serum resistance factors against sepsis of Acinetobacter baumannii [J ] . Microb Pathog, 2019, 131: 9-14. DOI: 10.1016/j.micpath.2019.03.031..
SINGH R, CAPALASH N, SHARMA P. Immunoprotective potential of BamA , the outer membrane protein assembly factor, against MDR Acinetobacter baumannii [J ] . Sci Rep, 2017, 7(1): 12411. DOI: 10.1038/s41598-017-12789-3..
GARG N, SINGH R, SHUKLA G, et al . Immunoprotective potential of in silico predicted Acinetobacter baumannii outer membrane nuclease, NucAb[J ] . Int J Med Microbiol, 2016, 306(1): 1-9. DOI: 10.1016/j.ijmm.2015.10.005..
SINGH R, GARG N, SHUKLA G, et al . Immunoprotective efficacy of Acinetobacter baumannii outer membrane protein, FilF, predicted in silico as a potential vaccine candidate[J ] . Front Microbiol, 2016, 7: 158. DOI: 10.3389/fmicb.2016.00158..
KING L B, PANGBURN M K, MCDANIEL L S. Serine protease PKF of Acinetobacter baumannii results in serum resistance and suppression of biofilm formation[J ] . J Infect Dis, 2013, 207(7): 1128-1134. DOI: 10.1093/infdis/jis939.
PULENDRAN B, S ARUNACHALAM P, O'HAGAN D T. Emerging concepts in the science of vaccine adjuvants[J]. Nat Rev Drug Discov, 2021, 20(6): 454-475. DOI: 10.1038/s41573-021-00163-y.
DA HORA V P, CONCEIÇÃO F R, DELLAGOSTIN O A, et al . Non-toxic derivatives of LT as potent adjuvants[J ] . Vaccine, 2011, 29(8): 1538-1544. DOI: 10.1016/j.vaccine.2010.11.091.
MAO L, LIU C, LIU J Y, et al . Novel synthetic lipopeptides as potential mucosal adjuvants enhanced SARS-CoV-2 rRBD-induced immune response[J ] . Front Immunol, 2022, 13: 833418. DOI: 10.3389/fimmu.2022.833418.
LYCKE N. Recent progress in mucosal vaccine development: potential and limitations[J]. Nat Rev Immunol, 2012, 12(8): 592-605. DOI: 10.1038/nri3251.
SOLTANI SHIRAZI A, AZIZI O, BOLOURCHI N, et al . Comparative in silico analyses of proteins involved inserum resistance as promising vaccine candidates against Acinetobacter baumannii [J ] . Vacres, 2017, 4(3): 64-71. DOI: 10.29252/vacres.4.3.4.64..
AWATE S, BABIUK L A, MUTWIRI G. Mechanisms of action of adjuvants[J]. Front Immunol, 2013, 4: 114. DOI: 10.3389/fimmu.2013.00114.
0
浏览量
0
下载量
0
CSCD
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
