用 mRNA DTP 疫苗对大鼠进行免疫可预防百日咳。

IF 2.9 3区 医学 Q3 IMMUNOLOGY
Infection and Immunity Pub Date : 2024-08-13 Epub Date: 2024-07-17 DOI:10.1128/iai.00520-23
Graham J Bitzer, Nicholas A Fitzgerald, Megan A DeJong, Casey Cunningham, Joshua A Chapman, Dylan T Boehm, Gage M Pyles, Annalisa B Huckaby, Sarah J Miller, Spencer R Dublin, Matthew D Warden, Mariette Barbier, F Heath Damron
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引用次数: 0

摘要

百日咳杆菌是一种革兰氏阴性细菌,是百日咳这种呼吸道疾病的病原体。自从改用 DTaP 和 Tap 无细胞疫苗以来,美国的百日咳病例呈上升和周期性下降趋势。我们观察到 mRNA 百日咳疫苗对小鼠具有免疫原性和保护性。在此,我们进一步评估了百日咳类毒素 mRNA 抗原,并根据百日咳毒素在体内的最佳中和效果改进了配方。接下来,我们使用百日咳杆菌气溶胶挑战模型和全身胸透监测咳嗽和呼吸功能,在 Sprague-Dawley 大鼠体内对 mRNA 百日咳疫苗进行了评估。雌性 Sprague-Dawley 大鼠接种了市售疫苗(DTaP 或 wP-DTP)、mRNA-DTP 疫苗或模拟接种疫苗。mRNA-DTP 疫苗对大鼠具有免疫原性,诱导的抗原特异性 IgG 抗体与 DTaP 相当。然后用耐链霉素的新临床分离物 D420Sm1 对大鼠进行气溶胶挑战。在挑战后第 1 天和第 9 天对细菌负荷进行评估,mRNA 疫苗减少的负荷与 DTaP 和 wP-DTP 相当。全身胸透显示,接种了 mRNA-DTP 疫苗的大鼠在咳嗽方面得到了很好的保护,与未接种组相当。这些数据表明,mRNA-DTP 疫苗在大鼠体内具有免疫原性,可保护 Sprague-Dawley 大鼠免受百日咳杆菌气溶胶感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Immunization with an mRNA DTP vaccine protects against pertussis in rats.

Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats.

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来源期刊
Infection and Immunity
Infection and Immunity 医学-传染病学
CiteScore
6.00
自引率
6.50%
发文量
268
审稿时长
3 months
期刊介绍: Infection and Immunity (IAI) provides new insights into the interactions between bacterial, fungal and parasitic pathogens and their hosts. Specific areas of interest include mechanisms of molecular pathogenesis, virulence factors, cellular microbiology, experimental models of infection, host resistance or susceptibility, and the generation of innate and adaptive immune responses. IAI also welcomes studies of the microbiome relating to host-pathogen interactions.
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