Adjuvant activity of non-ionic block copolymers. V. Modulation of antibody isotype by lipopolysaccharides, lipid A and precursors.
Adjuvant activity of non-ionic block copolymers. V. Modulation of antibody isotype by lipopolysaccharides, lipid A and precursors.
复制标题
非离子嵌段共聚物的佐剂活性。
DOI：
10.1016/0264-410x(91)90109-j
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发表时间：
1991
期刊：
影响因子：
5.5
通讯作者：
Hunter,RL
中科院分区：
文献类型：
--
作者：
Takayama,K;Olsen,M;Datta,P;Hunter,RL
非离子嵌段共聚物和脂多糖都是有效的免疫佐剂，被认为通过不同的机制起作用。我们假设它们一起使用时可能产生协同效应。我们制备了一系列脂多糖（LPS）制剂，范围从最小的前体，脂质X通过完整的LPS与O-多糖链。还使用了三种毒性降低的制剂，单磷酰脂质A，部分水解的Ra-LPS和红球藻球形LPS。所有的LPS制剂，除了最小的是有效的佐剂诱导早期抗体反应，三硝基苯基共轭鸡蛋白蛋白（TNP-HEA）时，在角鲨烷的水乳液与共聚物L141注射。只有较大的LPS制剂诱导持续的抗体应答。共聚物L141的乳液本身诱导主要的IgG 1抗体同种型应答，而IgG 2a和IgG 2b的量较少。令人惊讶的是，所有测试的LPS制剂都增加了IgG 2同种型的比例，即使有些对总体滴度几乎没有影响。脱毒的Ra-LPS（Ra-detox）是增加抗体滴度和诱导所需IgG 2a和IgG 2b同种型的最有效的制剂。这些结果表明LPS和嵌段聚合物佐剂的组合可以产生协同效应而没有不可接受的毒性。
Non-ionic block copolymers and lipopolysaccharides are both effective immunological adjuvants which are thought to act via distinct mechanisms. We hypothesized that they might produce synergistic effects when used together. We prepared a series of lipopolysaccharide (LPS) preparations ranging from the smallest precursor, lipid X through complete LPS with O-polysaccharide chains. Three preparations with reduced toxicity, monophosphoryl lipid A, partially hydrolysed Ra-LPS and LPS ofRhodopseudomonas sphaeroideswere also utilized. All LPS preparations except the smallest were effective adjuvants for inducing early antibody responses to trinitrophenyl-conjugated hen egg albumin (TNP-HEA) when injected in squalane-in-water emulsions with copolymer L141. Only the larger LPS preparations induced sustained antibody responses. By itself, emulsions of copolymer L141 induced a predominant IgG1 antibody isotype response with lesser amounts of IgG2a and IgG2b. Surprisingly, all of the LPS preparations tested increased the proportion of IgG2 isotypes even though some had little effect on overall titres. The detoxified Ra-LPS (Ra-detox) was the most effective preparation for both increasing antibody titres and inducing the desirable IgG2a and IgG2b isotypes. These results demonstrate that the combination of LPS and block polymer adjuvants can produce synergistic effects without unacceptable toxicities.