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肺炎克雷伯菌生物共轭疫苗在小鼠体内的功能持久性

Klebsiella pneumoniae bioconjugate vaccine functional durability in mice.

作者信息

Wantuch Paeton L, Knoot Cory J, Marino Emily C, Harding Christian M, Rosen David A

机构信息

Department of Pediatrics, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110, USA.

Omniose, St. Louis, MO 63110, USA.

出版信息

Vaccine. 2025 Jan 1;43(Pt 2):126536. doi: 10.1016/j.vaccine.2024.126536. Epub 2024 Nov 20.

DOI:10.1016/j.vaccine.2024.126536
PMID:39571358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12079703/
Abstract

Klebsiella pneumoniae is a leading cause of hospital-acquired infections as well as the leading cause of neonatal sepsis worldwide. Further, increasing antibiotic resistance in this pathogen makes K. pneumoniae troublesome to treat. Despite its clinical importance, there is not yet an approved K. pneumoniae vaccine available. Here we tested antibody durability and long-term functionality of two previously reported bioconjugate vaccines targeting the K. pneumoniae capsular type K2 and O-antigen type O1v1. We demonstrate that both antibodies are durable in mice for up to six months with significant IgG titers. However, only the K2 antibodies exhibit functionality out to six months as evidenced by serum bactericidal activity and survival in a murine bacteremia challenge model. These results are another promising step towards demonstrating the clinical capacity of bioconjugate vaccines and their induction of durable antibody responses.

摘要

肺炎克雷伯菌是医院获得性感染的主要原因,也是全球新生儿败血症的主要原因。此外,这种病原体中抗生素耐药性的增加使得肺炎克雷伯菌难以治疗。尽管其具有临床重要性,但目前尚无获批的肺炎克雷伯菌疫苗。在此,我们测试了两种先前报道的针对肺炎克雷伯菌荚膜K2型和O抗原O1v1型的生物偶联疫苗的抗体持久性和长期功能。我们证明,两种抗体在小鼠体内可持续长达六个月,具有显著的IgG滴度。然而,只有K2抗体在六个月后仍表现出功能,这在血清杀菌活性和小鼠菌血症攻击模型中的存活率中得到了证明。这些结果是朝着证明生物偶联疫苗的临床能力及其诱导持久抗体反应迈出的又一充满希望的一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/83beb9d36aeb/nihms-2077684-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/215be91088c2/nihms-2077684-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/16eabb992445/nihms-2077684-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/83029dbee1c8/nihms-2077684-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/83beb9d36aeb/nihms-2077684-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/215be91088c2/nihms-2077684-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/16eabb992445/nihms-2077684-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/83029dbee1c8/nihms-2077684-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f002/12079703/83beb9d36aeb/nihms-2077684-f0004.jpg

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Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.撒哈拉以南非洲和南亚地区肺炎克雷伯菌导致的儿童死亡:儿童健康和死亡率监测(CHAMPS)数据的二次分析。
Lancet Microbe. 2024 Feb;5(2):e131-e141. doi: 10.1016/S2666-5247(23)00290-2. Epub 2024 Jan 11.
3
Klebsiella pneumoniae: adaptive immune landscapes and vaccine horizons.
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Trends Immunol. 2023 Oct;44(10):826-844. doi: 10.1016/j.it.2023.08.005. Epub 2023 Sep 11.
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Causes of Death Among Infants and Children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network.儿童健康与死亡率监测(CHAMPS)网络中婴儿和儿童的死亡原因。
JAMA Netw Open. 2023 Jul 3;6(7):e2322494. doi: 10.1001/jamanetworkopen.2023.22494.
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