High Potency of Novel Polymeric Adjuvant in Eliciting of the Immune Response in Mice to Major Antigens of Chlamydia and Yersinia

V.A. Feodorov , A.M. Lyapina , O.V. Ulianova , T.I. Polyanina , Yu.Yu. Eliseev , V.L. Motin
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Abstract

Polyoxidonium (PO) has been recognized as an effective, safe immunomodulator with a marked immuno-stimulating activity suitable for the complex treatment of both acute and chronic infections in humans. The PO contains high-polymeric units of 100 kDa based on both N-oxide 1,4- ethylene piperazine and (N-carboxyethyl-) 1,4 ethylene piperazine bromide. Recently, PO has been licensed for human use in the new Russian trivalent polymeric subunit flu vaccine “Grippol.” This will open a possibility of using the PO for the development of vaccines against other infectious diseases. Here we studied the potency of the PO in eliciting the humoral immune response to specific antigens of Chlamydia spp. (C1 and C2) and Yersinia pestis (Pla, LcrV, and YopM) in comparison with the Freund's complete (FCA) and Titermax (TMC) adjuvants. The Balb/c mice were primed with a single intraperitoneal injection of the 10-20 μg of antigen mixed 1:1 with either adjuvant and boosted 3 times with the same antigen alone. We found at least 8- to 16-fold and 4- to 8-fold increases in IgG titers to Chlamydia and Yersinia antigens, respectively, after injections of the antigens with the PO in relation to the use of the either FCA or TMC. The PO was found to be absolutely safe for animal health, since there were no visible adverse reactions at the inoculation site characteristic of those seen with the other adjuvants, in particular FCA. Thus, the PO could be the adjuvant of choice to elicit a strong immune response to the major antigens of Chlamydia and Yersinia, suggesting the possibility of its use in developing bi- and tri-valent subunit vaccines with enhanced immunity. The exact mechanism of priming the immune response by the PO is under investigation.

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新型高效聚合佐剂诱导小鼠对衣原体和耶尔森氏菌主要抗原的免疫应答
多氧化铵(PO)已被认为是一种有效、安全的免疫调节剂,具有显著的免疫刺激活性,适用于人类急性和慢性感染的复杂治疗。PO含有基于n -氧化物1,4-乙烯哌嗪和(n -羧基乙基-)1,4-乙烯哌嗪溴的100 kDa的高分子单元。最近,PO已获准用于新的俄罗斯三价聚合亚基流感疫苗“Grippol”。这将使利用PO开发针对其他传染病的疫苗成为可能。在这里,我们研究了PO在诱导对衣原体(C1和C2)和鼠疫耶尔森氏菌(Pla, LcrV和YopM)特异性抗原的体液免疫应答方面的效力,并与Freund’s complete (FCA)和Titermax (TMC)佐剂进行了比较。将10-20 μg的抗原与任一佐剂1:1混合,单次腹腔注射Balb/c小鼠,并将同一抗原单独增强3次。我们发现,与使用FCA或TMC相比,在注射含有PO的抗原后,对衣原体和耶尔森氏菌抗原的IgG滴度分别增加了至少8- 16倍和4- 8倍。研究发现,PO对动物健康是绝对安全的,因为在接种部位没有其他佐剂(尤其是FCA)所特有的明显不良反应。因此,PO可能是引起对衣原体和耶尔森氏菌主要抗原的强烈免疫应答的首选佐剂,这表明它有可能用于开发具有增强免疫力的双价和三价亚单位疫苗。PO引发免疫反应的确切机制尚在研究中。
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