M2e conjugated gold nanoparticle influenza vaccine displays thermal stability at elevated temperatures and confers protection to ferrets.
M2e conjugated gold nanoparticle influenza vaccine displays thermal stability at elevated temperatures and confers protection to ferrets.
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M2e结合的金纳米颗粒流感疫苗在升高的温度下显示出热稳定性，并赋予雪貂保护。
DOI：
10.1016/j.vaccine.2021.07.032
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发表时间：
2021-08-09
期刊：
影响因子：
5.5
通讯作者：
Gill HS
中科院分区：
文献类型：
--
作者：
Ingrole RSJ;Tao W;Joshi G;Gill HS
目前批准的流感疫苗不仅保护范围有限，而且在适当条件下(2-8摄氏度)储存时的保质期也有限，为12-18个月。在制造、运输、分发直至交付给患者的过程中，储存温度的无意改变可能会损坏疫苗，从而降低其效力。热稳定的疫苗可以通过减少对冷藏系统的依赖来减少经济负担，还可以通过允许运输到世界上冷藏条件稀缺的偏远地区来加强疫苗接种计划的推广。我们之前已经开发出一种广泛保护性的甲型流感疫苗，方法是将甲型流感病毒基质2蛋白(M2e)的高度保守的胞外区连接到金纳米颗粒(AuNPs)上，随后添加Toll样受体9激动剂CpG作为佐剂，在小鼠模型中显示了其广泛的保护作用。在这项研究中，我们表明疫苗在4°C保存3个月、37°C保存3个月和50°C冷冻干燥2周时是热稳定的，后来可以很容易地在水中重建它而不会聚集。重组疫苗滴鼻免疫小鼠，诱导出与新鲜疫苗相似的血清中M2e特异性免疫球蛋白和免疫球蛋白亚型，并完全保护小鼠免受致命的甲型流感攻击。该疫苗经鼻腔或肌肉免疫雪貂，可诱导出M2e特异性免疫球蛋白G，经鼻腔免疫的雪貂鼻腔冲洗液中病毒水平降低。
Currently approved influenza vaccines are not only limited in breadth of protection but also have a limited shelf-life of 12–18 months when stored under appropriate conditions (2–8 °C). Inadvertent alteration in storage temperatures during manufacturing, transportation, distribution until delivery to patient, can damage the vaccine thus reducing its efficacy. A thermally stable vaccine can decrease the economic burden by reducing reliance on refrigeration system and can also enhance outreach of the vaccination program by allowing transportation to remote areas of the world where refrigerated conditions are scarce. We have previously developed a broadly protective influenza A vaccine by coupling the highly conserved extracellular region of the matrix 2 protein (M2e) of influenza A virus to gold nanoparticles (AuNPs) and upon subsequent addition of toll-like receptor 9 agonist – CpG, as an adjuvant, have shown its breadth of protection in a mouse model. In this study, we show that the vaccine is thermally stable when stored at 4 °C for 3 months, 37 °C for 3 months and 50 °C for 2 weeks in its lyophilized form, and later it was possible to readily reconstitute it in water without aggregation. Intranasal vaccination of mice using reconstituted vaccine induced M2e-specific IgG and IgG subtypes in serum similar to the freshly formulated vaccine, and fully protected mice against lethal influenza A challenge. Immunization of ferrets intranasally or intramuscularly with the vaccine induced M2e-specific IgG and there was reduced virus level in nasal wash of ferrets immunized through intranasal route.
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金纳米粒子-M2E与CPG共轭偶联物可诱导对流感病毒的保护性免疫。
DOI：
10.2217/nnm.13.58
发表时间：
2014-02
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Tao W;Ziemer KS;Gill HS
通讯作者：
Gill HS
DOI：
10.1089/108729001753231713
发表时间：
2001-10-01
期刊：
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
影响因子：
--
作者：
Rankin, R;Pontarollo, R;van den Hurk, LV
通讯作者：
van den Hurk, LV
影响因子：
5.5
作者：
Huang, J;Garmise, RJ;Sullivan, VJ
通讯作者：
Sullivan, VJ
影响因子：
3.7
作者：
Enkirch T;von Messling V
通讯作者：
von Messling V
影响因子：
5.4
作者：
Fang, Yuan;Rowe, Thomas;Kelvin, David J.
通讯作者：
Kelvin, David J.