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II型不耐热肠毒素与两种不同候选蓖麻毒素疫苗抗原联合使用的比较佐剂效应

Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.

作者信息

Vance David J, Greene Christopher J, Rong Yinghui, Mandell Lorrie M, Connell Terry D, Mantis Nicholas J

机构信息

Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA.

Department of Microbiology and Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, The University at Buffalo, Buffalo, New York, USA.

出版信息

Clin Vaccine Immunol. 2015 Dec;22(12):1285-93. doi: 10.1128/CVI.00402-15. Epub 2015 Oct 21.

Abstract

Type II heat-labile enterotoxins (HLTs) constitute a promising set of adjuvants that have been shown to enhance humoral and cellular immune responses when coadministered with an array of different proteins, including several pathogen-associated antigens. However, the adjuvant activities of the four best-studied HLTs, LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc, have never been compared side by side. We therefore conducted immunization studies in which LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc were coadministered by the intradermal route to mice with two clinically relevant protein subunit vaccine antigens derived from the enzymatic A subunit (RTA) of ricin toxin, RiVax and RVEc. The HLTs were tested with low and high doses of antigen and were assessed for their abilities to stimulate antigen-specific serum IgG titers, ricin toxin-neutralizing activity (TNA), and protective immunity. We found that all four HLTs tested were effective adjuvants when coadministered with RiVax or RVEc. LT-IIa was of particular interest because as little as 0.03 μg when coadministered with RiVax or RVEc proved effective at augmenting ricin toxin-specific serum antibody titers with nominal evidence of local inflammation. Collectively, these results justify the need for further studies into the mechanism(s) underlying LT-IIa adjuvant activity, with the long-term goal of evaluating LT-IIa's activity in humans.

摘要

II型热不稳定肠毒素(HLTs)是一类很有前景的佐剂,已证明当与一系列不同蛋白质(包括几种病原体相关抗原)共同给药时,它们能增强体液免疫和细胞免疫反应。然而,四种研究最深入的HLTs,即LT-IIa、LT-IIb、LT-IIb(T13I)和LT-IIc的佐剂活性从未被同时比较过。因此,我们进行了免疫研究,通过皮内途径将LT-IIa、LT-IIb、LT-IIb(T13I)和LT-IIc与两种临床相关的蛋白质亚单位疫苗抗原(源自蓖麻毒素的酶A亚基(RTA),即RiVax和RVEc)共同给予小鼠。对HLTs进行了低剂量和高剂量抗原测试,并评估了它们刺激抗原特异性血清IgG滴度、蓖麻毒素中和活性(TNA)和保护性免疫的能力。我们发现,与RiVax或RVEc共同给药时,所有四种测试的HLTs都是有效的佐剂。LT-IIa特别令人感兴趣,因为与RiVax或RVEc共同给药时,低至0.03μg就被证明能有效提高蓖麻毒素特异性血清抗体滴度,且几乎没有局部炎症迹象。总体而言,这些结果证明有必要进一步研究LT-IIa佐剂活性的潜在机制,其长期目标是评估LT-IIa在人体中的活性。

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