Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system. In the current study, a squalene based adjuvant (AddaVax, InvivoGen, San Diego, Ca) equivalent to the clinically approved MF59 (Seqiris, Maidenhead, UK) elicited greater antibody responses in mice than the previously employed adjuvant polyinosinic:polycytidylic acid, ((poly(I:C), InvivoGen, San Diego, Ca) and the clinically approved Aluminum hydroxide gel (Alum, Invivogen, San Diego, Ca) adjuvant. Use of the AddaVax adjuvant also expanded the range of IgG subtypes elicited by mouse vaccination. Sera passively transferred into mice from MCSP/AddaVax immunized one and six month old macaques significantly reduced liver sporozoite load upon sporozoite challenge. Protective antibody concentrations attained by passive transfer in the mice were equivalent to those observed in infant macaques 18 weeks after the final immunization. The efficacy of this vaccine in a relevant non-human primate model indicates its potential usefulness for the analogous high risk human population.

中文翻译：

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抗原融合到配体上的未成熟树突状细胞受体疫苗引起婴儿猕猴疟疾子孢子的抗体反应升高。

婴儿和幼儿是恶性疟原虫感染导致严重疾病的最大风险人群。先前我们在小鼠中证明了由趋化因子巨噬细胞炎症蛋白3α遗传融合至恶性疟原虫的最小截短环子孢子蛋白（MCSP）组成的蛋白疫苗在小鼠模型系统中引起高浓度的特异性抗体并显着降低了肝子孢子的载量。在当前的研究中，与临床上批准的MF59（Seqiris，Maidenhead，UK）等效的基于角鲨烯的佐剂（AddaVax，InvivoGen，San Diego，Ca）与先前使用的佐剂多肌苷酸：多胞苷酸（聚（I：C），InvivoGen（加利福尼亚州圣地亚哥）和临床认可的氢氧化铝凝胶（明矾，Invivogen，圣地亚哥，Ca）佐剂。AddaVax佐剂的使用也扩大了小鼠接种疫苗引发的IgG亚型的范围。从接种了1个月和6个月大猕猴的MCSP / AddaVax被动转移到小鼠体内的血清可在子孢子攻击后显着降低肝脏的子孢子负荷。在小鼠中通过被动转移获得的保护性抗体浓度与最终免疫后18周在婴儿猕猴中观察到的浓度相等。该疫苗在相关的非人类灵长类动物模型中的功效表明了其对类似的高危人群的潜在有用性。从接种了1个月和6个月大猕猴的MCSP / AddaVax被动转移到小鼠体内的血清可在子孢子攻击后显着降低肝脏的子孢子负荷。在小鼠中通过被动转移获得的保护性抗体浓度与最终免疫后18周在婴儿猕猴中观察到的浓度相等。该疫苗在相关的非人类灵长类动物模型中的功效表明其对类似的高危人群的潜在用途。从接种了1个月和6个月大猕猴的MCSP / AddaVax被动转移到小鼠体内的血清可在子孢子攻击后显着降低肝脏的子孢子负荷。在小鼠中通过被动转移获得的保护性抗体浓度与最终免疫后18周在婴儿猕猴中观察到的浓度相等。该疫苗在相关的非人类灵长类动物模型中的功效表明其对类似的高危人群的潜在用途。