一种针对未成熟树突状细胞的趋化因子融合疫苗可在婴儿恒河猴中引发针对疟疾子孢子的高抗体应答。

A chemokine-fusion vaccine targeting immature dendritic cells elicits elevated antibody responses to malaria sporozoites in infant macaques.

机构信息

The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.

出版信息

Sci Rep. 2021 Jan 13;11(1):1220. doi: 10.1038/s41598-020-79427-3.

Abstract

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 1 and 6 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.

摘要

婴儿和幼儿是因恶性疟原虫感染而导致严重疾病的高危人群。我们之前在小鼠中证明,一种由趋化因子巨噬细胞炎症蛋白 3α与恶性疟原虫最小截短环子孢子蛋白(MCSP)基因融合而成的蛋白疫苗,可在小鼠模型系统中引发高浓度的特异性抗体,并显著减少肝脏疟原虫孢子负荷。在当前的研究中,一种角鲨烯佐剂(AddaVax,InvivoGen,圣地亚哥,加利福尼亚州)与临床批准的 MF59(Seqiris,梅登黑德,英国)等效,比之前使用的佐剂聚肌苷酸:聚胞苷酸((poly(I:C),InvivoGen,圣地亚哥,加利福尼亚州)和临床批准的氢氧化铝凝胶(Alum,Invivogen,圣地亚哥,加利福尼亚州)佐剂能引发更多的抗体反应。AddaVax 佐剂的使用还扩大了通过小鼠疫苗接种引发的 IgG 亚型范围。从 MCSP/AddaVax 免疫的 1 个月和 6 个月大的猕猴被动转移到小鼠的血清显著降低了在疟原虫孢子攻击时的肝脏疟原虫孢子负荷。在小鼠中通过被动转移获得的保护性抗体浓度与最后一次免疫后 18 周的婴儿猕猴中观察到的浓度相当。这种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风险人类人群具有潜在的用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5199/7807052/01bac7609a84/41598_2020_79427_Fig1_HTML.jpg

相似文献

本文引用的文献

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索