Authorization of the Matrix-M (MM)–adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23–week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8–week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and T H 2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines.

中文翻译：

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R21 疟疾疫苗多种临床阶段佐剂在非人灵长类动物中的比较免疫学评估


Matrix-M (MM) 佐剂 R21 疫苗获得三个国家的授权以及随后世界卫生组织对儿童疟疾预防的认可，是抗击疟疾的一个里程碑。然而，我们对这种疫苗引起的先天性和适应性免疫反应的了解仍然有限。在这里，我们比较了三种临床相关佐剂[3M-052 + 氢氧化铝（明矾）(3M)，一种以明矾配制的 TLR7/8 激动剂； GLA-LSQ，一种与 QS-21 配制在脂质体中的 TLR4 激动剂； MM，现已批准的 R21 佐剂]，因为它们能够在猕猴中诱导针对 R21 的持久免疫反应。按 0、8 和 23 周方案添加 3M 佐剂的 R21 引发的抗环子孢子抗体反应的程度与使用 0-4-8 周方案施用的 R21/MM 疫苗相当，并且持续长达 72 周，半数-寿命337天。 72 周时的加强剂量可引起类似于 R21/MM 疫苗接种的回忆反应。相比之下，R21/GLA-LSQ 免疫在所用剂量下诱导的反应较低且短暂。与持久的血清抗体反应一致，MM 和 3M 在骨髓和其他组织（包括脾脏）中诱导了长寿的浆细胞。此外，3M 在初次免疫和加强免疫后刺激了有效且持久的抗病毒转录和细胞因子特征，而 MM 在加强免疫后诱导了干扰素和 TH 2 相关特征表达的增强。总的来说，这些发现为 R21 的三种临床相关佐剂的免疫反应提供了资源，并强调了 3M 作为另一种疟疾疫苗佐剂的前景。