Denis-Mize Kimberly S, Dupuis Marc, Singh Manmohan, Woo Carolyn, Ugozzoli Mildred, O'Hagan Derek T, Donnelly John J, Ott Gary, McDonald Donald M
Department of Anatomy and Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA.
Cell Immunol. 2003 Sep;225(1):12-20. doi: 10.1016/j.cellimm.2003.09.003.
Investigation into the mechanism of action of vaccine adjuvants provides opportunities to define basic immune principles underlying the induction of strong immune responses and insights useful for the rational development of subunit vaccines. A novel HIV vaccine composed of plasmid DNA-encoding p55 gag formulated with poly-lactide-co-glycolide microparticles (PLG) and cetyl trimethyl ammonium bromide (CTAB) elicits both serum antibody titers and cytotoxic lymphocyte activity in mice at doses two orders of magnitude lower than those required for comparable response to plasmid DNA in saline. Using this model, we demonstrated the increase in potency requires the DNA to be complexed to the PLG-CTAB microparticles. Furthermore, the PLG-CTAB-DNA formulation increased the persistence of DNA at the injection site, recruited mononuclear phagocytes to the site of injection, and activated a population of antigen presenting cells. Intramuscular immunization with the PLG-CTAB-DNA complex induced antigen expression at both the injection site and the draining lymph node. These findings demonstrate that the PLG-CTAB-DNA formulation exhibits multiple mechanisms of immunopotentiation.
对疫苗佐剂作用机制的研究为确定诱导强烈免疫反应的基本免疫原理提供了机会，并为亚单位疫苗的合理开发提供了有用的见解。一种新型的HIV疫苗，由编码p55 gag的质粒DNA与聚乳酸-乙醇酸微粒（PLG）和十六烷基三甲基溴化铵（CTAB）配制而成，在小鼠体内引发血清抗体滴度和细胞毒性淋巴细胞活性，所需剂量比在盐水中对质粒DNA产生类似反应所需剂量低两个数量级。利用这个模型，我们证明了效力的提高需要DNA与PLG-CTAB微粒复合。此外，PLG-CTAB-DNA制剂增加了DNA在注射部位的持久性，将单核吞噬细胞募集到注射部位，并激活了一群抗原呈递细胞。用PLG-CTAB-DNA复合物进行肌肉内免疫在注射部位和引流淋巴结均诱导了抗原表达。这些发现表明，PLG-CTAB-DNA制剂表现出多种免疫增强机制。
