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基因工程减毒活疫苗诱导的针对感染的长期保护性免疫

Long-Term Protective Immunity against Infection Induced by a Genetically Modified Live Vaccine.

作者信息

Madesh Swetha, McGill Jodi, Jaworski Deborah C, Ferm Jonathan, Liu Huitao, Fitzwater Shawna, Hove Paidashe, Ferm Dominica, Nair Arathy, Knox Cheyenne A, Alizadeh Kimia, Thackrah Ashley, Ganta Roman R

机构信息

Center of Excellence for Vector-Borne Diseases, Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA.

Department of Veterinary Pathobiology, College of Veterinary Medicine, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.

出版信息

Vaccines (Basel). 2024 Aug 9;12(8):903. doi: 10.3390/vaccines12080903.

DOI:10.3390/vaccines12080903
PMID:39204029
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11360114/
Abstract

Human monocytic ehrlichiosis, an emerging tick-borne disease, is caused by . Infections with the pathogen are also common in the canine host. Our previous studies demonstrated that functional disruption within the phage head-to-tail connector protein gene results in bacterial attenuation, creating a modified live attenuated vaccine (MLAV). The MLAV confers protective immunity against intravenous and tick transmission challenges one month following vaccination. In this study, we evaluated the duration of MLAV protection. Dogs vaccinated with the MLAV were challenged with wild-type via intravenous infection at 4-, 8-, and 12-months post-vaccination. Immunized dogs rapidly cleared the wild-type pathogen infection and tested positive for bacteremia less frequently than unvaccinated controls. While immune responses varied among dogs, vaccinees consistently mounted IgG and CD4+ T-cell responses specific to throughout the assessment period. Our findings demonstrate that MLAV-mediated immune protection persists for at least one year against wild-type bacterial infection, marking a major advancement in combating this serious tick-borne disease. The data presented here serve as the foundation for further studies, elucidating the molecular mechanisms underlying virulence and vaccine development and aiding in preventing the diseases caused by and other tick-borne rickettsial pathogens.

摘要

人单核细胞埃立克体病是一种新出现的蜱传疾病,由……引起。该病原体在犬类宿主中的感染也很常见。我们之前的研究表明,噬菌体头尾连接蛋白基因内的功能破坏会导致细菌减毒,从而产生一种新型活减毒疫苗(MLAV)。接种疫苗一个月后,MLAV能对静脉内感染和蜱传播攻击提供保护性免疫。在本研究中,我们评估了MLAV保护的持续时间。接种MLAV的犬在接种疫苗后4个月、8个月和12个月时通过静脉感染用野生型……进行攻击。免疫的犬迅速清除野生型病原体感染,菌血症检测呈阳性的频率低于未接种疫苗的对照组。虽然不同犬的免疫反应有所不同,但在整个评估期间,接种疫苗的犬始终产生针对……的IgG和CD4 + T细胞反应。我们的研究结果表明,MLAV介导的免疫保护对野生型细菌感染至少持续一年,这标志着在对抗这种严重蜱传疾病方面取得了重大进展。本文提供的数据为进一步研究奠定了基础,有助于阐明毒力和疫苗开发的分子机制,并有助于预防由……和其他蜱传立克次体病原体引起的疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/34fd653ae375/vaccines-12-00903-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/5eef64797264/vaccines-12-00903-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/17f7ad0f863a/vaccines-12-00903-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/be7841e7870e/vaccines-12-00903-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/f153e95813bc/vaccines-12-00903-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/34fd653ae375/vaccines-12-00903-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/5eef64797264/vaccines-12-00903-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/17f7ad0f863a/vaccines-12-00903-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/be7841e7870e/vaccines-12-00903-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/f153e95813bc/vaccines-12-00903-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f9f/11360114/34fd653ae375/vaccines-12-00903-g005.jpg

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