中文摘要：研究分别将佐剂Poly (I:C)、Poly (IC:LC)与呼吸道合胞体病毒（RSV）DS-Cav1稳定融合蛋白进行组合，评估不同佐剂的免疫反应。结果表明，采用Sigma佐剂系统（SAS）的聚羧乙烯水包油佐剂、2倍剂量的DS-Cav1免疫天然小鼠能够产生非常高的RSV中和抗体反应（19,006 EC50），而单独使用明矾Sigma佐剂系统（SAS）、Adjuplex、Poly (I:C)、Poly (IC:LC)能够产生较高的免疫反应（3658-7108），采用TLR4促进剂MPLA、明矾联合MPLA或AddaVax为佐剂能够产生中等免疫反应（1251-2129）。相反，单独使用DS-Cav1进行免疫产生的免疫反应水平较低。除明矾和Adjuplex佐剂组外，大多数高或者非常高的免疫试验组中诱导产生了平衡的IgG1和IgG2a(Th2/Th1)免疫反应。研究同时测定了经年小鼠的免疫反应，结果表明采用SAS和聚羧乙烯（Carbopol）联合佐剂能够促进免疫反应提高2-3倍，而明矾佐剂可以将免疫反应提高5倍。
 
外文摘要：Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50) were observed in naive mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I: C) and Poly (IC: LC); and moderate responses (1251-2129) were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex). We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the degree of adjuvant-induced enhancement appears to be both context-dependent and species-specific.
外文关键词：HUMAN-PAPILLOMAVIRUS TYPE-16; RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; REVERSE GENETICS; YOUNG-WOMEN; COTTON RATS; DISEASE; IMMUNIZATION; INFECTION; ALUM
作者：Sastry, M; Zhang, BS; Chen, M; Joyce, MG; Kong, WP; Chuang, GY; Ko, K; Kumar, A; Silacci, C; Thom, M; Salazar, AM; Corti, D; Lanzavecchia, A; Taylor, G; Mascola, JR; Graham, BS; Kwong, PD
作者单位：美国国立变态反应与传染病研究所
期刊名称：PLOS ONE
期刊影响因子：2.806
出版年份：2017
出版刊次：10
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