多价 mRNA-DTP 疫苗具有免疫原性,可保护小鼠免受百日咳博德特氏菌感染。

IF 6.9 1区 医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-06-10 DOI:10.1038/s41541-024-00890-4
M Allison Wolf, Joanne M O'Hara, Graham J Bitzer, Elisabeth Narayanan, Dylan T Boehm, Justin R Bevere, Megan A DeJong, Jesse M Hall, Ting Y Wong, Samantha Falcone, Cailin E Deal, Angelene Richards, Shannon Green, Brenda Nguyen, Emily King, Clinton Ogega, Lisa Russo, Emel Sen-Kilic, Obadiah Plante, Sunny Himansu, Mariette Barbier, Andrea Carfi, F Heath Damron
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引用次数: 0

摘要

百日咳细胞多价疫苗(DTaP 和 Tdap)可预防无症状疾病和婴儿死亡,但随着时间的推移,百日咳博德特氏菌感染的免疫力会明显减弱,导致百日咳周期性流行。信使核糖核酸(mRNA)疫苗平台为解决复杂的细菌感染问题提供了一个机会,这种疫苗具有适应性强的特点,能产生 Th1 偏倚反应。本研究使用免疫原性和挑战模型来评估 mRNA 平台与针对百日咳杆菌抗原以及白喉和破伤风类毒素的多价疫苗制剂。mRNA制剂免疫具有免疫原性,可诱导抗原特异性抗体和Th1 T细胞反应。在受到历史或现代百日咳杆菌毒株的挑战时,6 价和 10 价 mRNA DTP 疫苗提供的保护相当于 1/20 人剂量的 DTaP 或全细胞百日咳疫苗。这些临床前小鼠研究共同说明了 mRNA 平台在多价细菌病原体疫苗方面的潜力。
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Multivalent mRNA-DTP vaccines are immunogenic and provide protection from Bordetella pertussis challenge in mice.

Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.

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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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