Silicone Oil-Based Nanoadjuvants as Candidates for a New Formulation of Intranasal Vaccines.
Silicone Oil-Based Nanoadjuvants as Candidates for a New Formulation of Intranasal Vaccines.
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DOI：
10.3390/vaccines9030234
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发表时间：
2021-03-08
期刊：
影响因子：
7.8
通讯作者：
Myc A
中科院分区：
文献类型：
--
作者：
Razim A;Pyclik M;Pacyga K;Górska S;Xu J;Olszewski MA;Gamian A;Myc A
许多传统疫苗是通过针头注射给药的，而大多数病原体主要通过粘膜表面入侵宿主。此外，肠外疫苗不足以诱导保护性的IgA抗体。粘膜免疫诱导局部和全身对病原体的反应，通常持续很长时间。因此，通过粘膜途径接种疫苗已被越来越多地探索。然而，粘膜疫苗需要强大的佐剂才能生效。尽管为开发安全和强大的粘膜疫苗佐剂做出了许多努力，但只有少数几种佐剂被批准用于人类配方。本研究的目的是设计、开发和表征新型硅油为基础的纳米佐剂候选鼻腔疫苗，具有成为粘膜佐剂的潜力。我们已经开发了一系列纳米佐剂候选药物(NAC)，基于明确定义的成分。NAC1、2和3基于硅油，但使用的洗涤剂和有机溶剂不同，这导致它们的液滴大小和Zeta电位不同。体外检测NaCS的细胞毒作用、肿瘤坏死因子α(Tumor Necrosis Factorα，肿瘤坏死因子)的诱生作用及对免疫细胞吞噬抗原的影响。用卵清蛋白(OVA)与小鼠鼻腔接种来验证NaCS的佐剂特性。NaC具有显著的稳定性，不需要任何特殊的储存条件。它们表现出生物粘附性，并影响模型蛋白被上皮细胞吞噬的程度。此外，它们在两次鼻腔给药后诱导高特异性抗OVA抗体效价。由硅油和阳离子洗涤剂组成的纳米佐剂候选物稳定性好，具有显著的佐剂性能，可用作鼻腔免疫佐剂。
Many conventional vaccines are administered via a needle injection, while most pathogens primarily invade the host via mucosal surfaces. Moreover, protective IgA antibodies are insufficiently induced by parenteral vaccines. Mucosal immunity induces both local and systemic response to pathogens and typically lasts for long periods of time. Therefore, vaccination via mucosal routes has been increasingly explored. However, mucosal vaccines require potent adjuvants to become efficacious. Despite many efforts to develop safe and robust adjuvants for mucosal vaccines, only a few have been approved for use in human formulations. The aim of our study was to design, develop and characterize new silicone oil-based nanoadjuvant candidates for intranasal vaccines with potential to become mucosal adjuvants. We have developed an array of nanoadjuvant candidates (NACs), based on well-defined ingredients. NAC1, 2 and 3 are based on silicone oil, but differ in the used detergents and organic solvents, which results in variations in their droplet size and zeta potential. NACs’ cytotoxicity, Tumor Necrosis Factor α (TNF-α) induction and their effect on antigen engulfment by immune cells were tested in vitro. Adjuvant properties of NACs were verified by intranasal vaccination of mice together with ovalbumin (OVA). NACs show remarkable stability and do not require any special storage conditions. They exhibit bio-adhesiveness and influence the degree of model protein engulfment by epithelial cells. Moreover, they induce high specific anti-OVA IgG antibody titers after two intranasal administrations. Nanoadjuvant candidates composed of silicone oil and cationic detergents are stable, exhibit remarkable adjuvant properties and can be used as adjuvants for intranasal immunization.
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DOI：
10.4049/jimmunol.1601775
发表时间：
2017-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Boyaka PN
通讯作者：
Boyaka PN
DOI：
10.1007/978-1-61779-513-8_4
发表时间：
2012-01-01
期刊：
MUCINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Kesimer, Mehmet;Sheehan, John K.
通讯作者：
Sheehan, John K.
影响因子：
6
作者：
Lee S;Nguyen MT
通讯作者：
Nguyen MT
影响因子：
5.8
作者：
Christensen, Dennis;Foged, Camilla;Nielsen, Hanne Morck
通讯作者：
Nielsen, Hanne Morck
影响因子：
5.5
作者：
Even-Or, Orli;Joseph, Aviva;Barenholz, Yechezkel
通讯作者：
Barenholz, Yechezkel