Persing David H, Coler Rhea N, Lacy Michael J, Johnson David A, Baldridge Jory R, Hershberg Robert M, Reed Steven G
Corixa, Suite 200, 1124 Columbia Street, Seattle, WA 98104, USA.
Trends Microbiol. 2002;10(10 Suppl):S32-7. doi: 10.1016/s0966-842x(02)02426-5.
Vaccine adjuvants based on the structure of lipid A, such as monophosphoryl lipid A (MLA), have proven to be safe and effective in inducing immune responses to heterologous proteins in animal and human vaccines. Recent work on the development of a recombinant vaccine for leishmaniasis has demonstrated that a clinical grade MLA formulation - MPL(R) adjuvant - is essential in the development of a protective response. Preliminary evidence suggests that MLA and a chemically distinct family of lipid A mimetics - the aminoalkyl glucosaminide 4-phosphates - act on Toll-like receptor 4 (TLR4). As TLR4 agonists, they have potent immunomodulatory effects when used both as vaccine adjuvants and as stand-alone products. Novel approaches to vaccine development could benefit from taking full advantage of the effects of these compounds on innate and adaptive responses.
基于脂多糖A结构的疫苗佐剂，如单磷酰脂多糖A（MLA），已被证明在动物和人类疫苗中诱导针对异源蛋白的免疫反应时是安全有效的。最近关于利什曼病重组疫苗研发的工作表明，临床级MLA制剂——MPL(R)佐剂——在产生保护性反应的研发中至关重要。初步证据表明，MLA和化学性质不同的一类脂多糖A模拟物——氨基烷基葡糖胺4-磷酸——作用于Toll样受体4（TLR4）。作为TLR4激动剂，它们在用作疫苗佐剂和单独产品时都具有强大的免疫调节作用。疫苗研发的新方法可以通过充分利用这些化合物对先天性和适应性反应的作用而受益。
