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恒河猴新生儿 BCG 疫苗接种和雾化 BCG 复种后免疫细胞群体动态。

Immune cell population dynamics following neonatal BCG vaccination and aerosol BCG revaccination in rhesus macaques.

机构信息

UK Health Security Agency, Porton Down, Salisbury, SP4 0JG, UK.

出版信息

Sci Rep. 2024 Jul 23;14(1):16993. doi: 10.1038/s41598-024-67861-6.

Abstract

The BCG vaccine is given to millions of children globally but efficacy wanes over time and differences in the immune systems between infants and adults can influence vaccine efficacy. To this end, 34 rhesus macaques were vaccinated with BCG within seven days of birth and blood samples were collected over 88 weeks for quantification of blood cell populations. Overall, the composition of cell populations did not change significantly between BCG vaccinated and unvaccinated groups, and that BCG vaccination did not perturb normal development. In comparison to adult macaques, higher numbers of CD4+ T-cells, Tregs and NK cells were measured in the infant age group, suggesting a potential bias towards immunosuppressive and innate immune populations. Antigen-specific IFNγ secreting cell frequencies in infant BCG vaccinated animals were detectable in peripheral blood samples for 36 weeks after vaccination but declined following this. To evaluate the long-term impact of infant BCG vaccination on subsequent revaccination with BCG, a pilot study of three adult macaques received an aerosol BCG revaccination approximately 3 years after their initial BCG vaccination as infants. This induced an increase in PPD-specific IFNγ secreting cells, and increased secretion of the cytokines IFNγ and IL-1β, following stimulation with other microorganisms, which are signals associated with trained innate immunity.

摘要

BCG 疫苗在全球范围内为数百万儿童接种,但随着时间的推移,其效力会逐渐减弱,婴儿和成人之间免疫系统的差异也会影响疫苗的效力。为此,34 只恒河猴在出生后 7 天内接种了 BCG,并在 88 周内采集血液样本,以定量检测血细胞群。总体而言,BCG 接种组和未接种组的细胞群组成没有显著变化,BCG 接种也没有干扰正常发育。与成年猕猴相比,婴儿组中 CD4+T 细胞、Tregs 和 NK 细胞的数量更高,这表明存在向免疫抑制和固有免疫群体的潜在偏向。婴儿 BCG 接种动物的抗原特异性 IFNγ 分泌细胞频率在接种后 36 周的外周血样本中可检测到,但在此之后下降。为了评估婴儿 BCG 接种对随后用 BCG 进行再次接种的长期影响,对 3 只成年猕猴进行了一项初步研究,这些猕猴在婴儿时期接受了 BCG 气溶胶再次接种,大约 3 年后。这诱导了 PPD 特异性 IFNγ 分泌细胞的增加,并在刺激其他微生物后增加了 IFNγ 和 IL-1β 等细胞因子的分泌,这是与训练有素的先天免疫相关的信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/772e/11266652/00813c98fa26/41598_2024_67861_Fig1_HTML.jpg

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