Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model.
Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model.
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ID93和脂基佐剂对小鼠模型结核分枝杆菌的预防作用。
DOI：
10.1371/journal.pone.0247990
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Coler RN
中科院分区：
文献类型：
--
作者：
Baldwin SL;Reese VA;Larsen SE;Beebe E;Guderian J;Orr MT;Fox CB;Reed SG;Coler RN
据估计，2019年有1000万人患上结核病，这凸显了预防疾病和减少传播的疫苗的必要性。我们当前研究的目的是在TB疾病的临床前小鼠模型中表征和测试由ID 93、多蛋白融合抗原和脂质体制剂[包括合成的TLR 4激动剂（吡喃葡萄糖基脂质佐剂，GLA）和QS-21]组成的预防性结核病疫苗。还将ID 93 +GLA-LSQ疫苗与高度表征的ID 93 +GLA-SE水包油乳剂佐剂进行了比较，这些研究也包括ID 93 +GLA-SE水包油乳剂佐剂。候选疫苗M72与佐剂AS 01 E（GlaxoSmithKline Biologicals）组合在减少进展为活动性疾病方面的最近成功是有希望的，并且使目前在TB疫苗管道中的实验性疫苗重新兴奋。AS 01 E佐剂在脂质体制剂中含有单磷酰脂质A（MPL）和QS-21（一种皂苷）。虽然AS 01 E作为已批准和实验性疫苗的组分已显示出有效的佐剂活性，但开发该佐剂系统的替代品对于满足未来疫苗需求的高需求将变得重要。此外，强效佐剂的替代来源将有助于满足结核病疫苗的需求[根据世卫组织2019年全球结核病报告，估计全球近四分之一的人口患有潜伏性结核分枝杆菌（Mt B）]，解决（a）商品成本，（B）商品供应，以及（c）提高抗Mt B亚单位疫苗的疗效。我们表明，ID 93 +GLA-SE（含有乳剂佐剂）和ID 93 +GLA-LSQ（含有脂质体佐剂）均诱导ID 93特异性TH 1细胞免疫，包括表达IFNγ、TNF和IL-2的CD 4 + CD 44 + T细胞（使用流式细胞术和细胞内细胞因子染色）和疫苗特异性IgG 2抗体应答（使用ELISA）。此外，ID 93 +GLA-SE和ID 93 +GLA-LSQ均有效降低感染Mtb的小鼠肺内的细菌负荷。基于该脂质体佐剂制剂的制剂可以提供AS 01佐剂系统的替代方案。
An estimated 10 million people developed tuberculosis (TB) disease in 2019 which underscores the need for a vaccine that prevents disease and reduces transmission. The aim of our current studies is to characterize and test a prophylactic tuberculosis vaccine comprised of ID93, a polyprotein fusion antigen, and a liposomal formulation [including a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant, GLA) and QS-21] in a preclinical mouse model of TB disease. Comparisons of the ID93+GLA-LSQ vaccines are also made to the highly characterized ID93+GLA-SE oil-in-water emulsion adjuvant, which are also included these studies. The recent success of vaccine candidate M72 combined with adjuvant AS01E (GlaxoSmithKline Biologicals) in reducing progression to active disease is promising and has renewed excitement for experimental vaccines currently in the TB vaccine pipeline. The AS01E adjuvant contains monophosphoryl lipid A (MPL) and QS-21 (a saponin) in a liposomal formulation. While AS01E has demonstrated potent adjuvant activity as a component of both approved and experimental vaccines, developing alternatives to this adjuvant system will become important to fill the high demand envisioned for future vaccine needs. Furthermore, replacement sources of potent adjuvants will help to supply the demand of a TB vaccine [almost one-quarter of the world’s population are estimated to have latent Mycobacterium tuberculosis (Mtb) according to the WHO 2019 global TB report], addressing (a) cost of goods, (b) supply of goods, and (c) improved efficacy of subunit vaccines against Mtb. We show that both ID93+GLA-SE (containing an emulsion adjuvant) and ID93+GLA-LSQ (containing a liposomal adjuvant) induce ID93-specific TH1 cellular immunity including CD4+CD44+ T cells expressing IFNγ, TNF, and IL-2 (using flow cytometry and intracellular cytokine staining) and vaccine-specific IgG2 antibody responses (using an ELISA). In addition, both ID93+GLA-SE and ID93+GLA-LSQ effectively decrease the bacterial load within the lungs of mice infected with Mtb. Formulations based on this liposomal adjuvant formulation may provide an alternative to AS01 adjuvant systems.
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影响因子：
7
作者：
Alving CR;Peachman KK;Rao M;Reed SG
通讯作者：
Reed SG
影响因子：
9.2
作者：
Coccia M;Collignon C;Hervé C;Chalon A;Welsby I;Detienne S;van Helden MJ;Dutta S;Genito CJ;Waters NC;Deun KV;Smilde AK;Berg RAVD;Franco D;Bourguignon P;Morel S;Garçon N;Lambrecht BN;Goriely S;Most RV;Didierlaurent AM
通讯作者：
Didierlaurent AM
影响因子：
4.4
作者：
Jellison, ER;Kim, SK;Welsh, RM
通讯作者：
Welsh, RM
DOI：
10.1016/b978-0-12-804019-5.00006-2
发表时间：
2017-01-01
期刊：
IMMUNOPOTENTIATORS IN MODERN VACCINES, 2ND EDITION
影响因子：
--
作者：
Fox, C. B.;Carter, D.;Reed, S. G.
通讯作者：
Reed, S. G.
影响因子：
17.1
作者：
Bertholet S;Ireton GC;Ordway DJ;Windish HP;Pine SO;Kahn M;Phan T;Orme IM;Vedvick TS;Baldwin SL;Coler RN;Reed SG
通讯作者：
Reed SG