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MINCLE 和 TLR9 激动剂协同诱导小鼠和非人灵长类动物产生 Th1/Th17 疫苗记忆和黏膜回忆。

MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates.

机构信息

Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen, Denmark.

Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB/IDMIT/UMR1184), 92265, Fontenay-aux-Roses & Kremlin Bicêtre, France.

出版信息

Nat Commun. 2024 Oct 17;15(1):8959. doi: 10.1038/s41467-024-52863-9.

DOI:10.1038/s41467-024-52863-9
PMID:39420177
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11487054/
Abstract

Development of new vaccines tailored for difficult-to-target diseases is hampered by a lack of diverse adjuvants for human use, and none of the currently available adjuvants induce Th17 cells. Here, we develop a liposomal adjuvant, CAF®10b, that incorporates Mincle and Toll-like receptor 9 agonists. In parallel mouse and non-human primate studies comparing to CAF® adjuvants already in clinical trials, we report species-specific effects of adjuvant composition on the quality and magnitude of the responses. When combined with antigen, CAF®10b induces Th1 and Th17 responses and protection against a pulmonary infection with Mycobacterium tuberculosis in mice. In non-human primates, CAF®10b induces higher Th1 responses and robust Th17 responses detectable after six months, and systemic and pulmonary Th1 and Th17 recall responses, in a sterile model of local recall. Overall, CAF®10b drives robust memory antibody, Th1 and Th17 vaccine-responses via a non-mucosal immunization route across both rodent and primate species.

摘要

针对难以靶向的疾病开发新疫苗受到缺乏适合人类使用的多种佐剂的阻碍，而目前可用的佐剂均不能诱导 Th17 细胞。在这里，我们开发了一种脂质体佐剂 CAF®10b，它结合了 Mincle 和 Toll 样受体 9 激动剂。在与已在临床试验中的 CAF®佐剂进行的平行小鼠和非人类灵长类动物研究中，我们报告了佐剂组成对反应质量和规模的物种特异性影响。当与抗原结合时，CAF®10b 在小鼠中诱导 Th1 和 Th17 反应，并预防结核分枝杆菌引起的肺部感染。在非人类灵长类动物中，CAF®10b 诱导更高的 Th1 反应和可检测到的六个月后强大的 Th17 反应，以及在局部回忆的无菌模型中全身和肺部 Th1 和 Th17 回忆反应。总体而言，CAF®10b 通过非黏膜免疫途径在啮齿动物和灵长类动物中引发强大的记忆抗体、Th1 和 Th17 疫苗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c77/11487054/8b7298ff9379/41467_2024_52863_Fig7_HTML.jpg
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