Gupta R K, Rost B E, Relyveld E, Siber G R
Massachusetts Public Health Biologic Laboratories, State Laboratory Institute, Boston, Massachusetts 02130, USA.
Pharm Biotechnol. 1995;6:229-48. doi: 10.1007/978-1-4615-1823-5_8.
It is likely that aluminum compounds will continue to be used with human vaccines for many years as a result of their excellent track record of safety and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminum adjuvants formulated under optimal conditions are the adjuvants of choice. It is important to select carefully the type of aluminum adjuvant and optimize the conditions of adsorption for every antigen since the degree of adsorption of antigens onto aluminum adjuvants markedly affects immunogenicity. The mechanism of adjuvanticity of aluminum compounds includes formation of a depot at the site of injection from which antigen is released slowly; stimulation of immune-competent cells of the body through activation of complement, induction of eosinophilia, and activation of macrophages; and efficient uptake of aluminum-adsorbed antigen particles by antigen-presenting cells because of their particulate nature and optimal size (< 10 microns). Limitations of aluminum adjuvants include local reactions, production of IgE antibodies, ineffectiveness for some antigens, and inability to elicit cell-mediated immune responses especially cytotoxic T-cell responses. Calcium phosphate, which has adjuvant properties similar to aluminum adjuvants, has the potential advantages of being a natural component of the body and of not increasing IgE production. There is a need for alternative adjuvants, particularly for diseases in which cell-mediated immune responses are important for prevention or cure.
由于铝化合物在与多种抗原结合时具有出色的安全性和佐剂活性记录，它们可能会在许多年内继续用于人类疫苗。对于可通过诱导血清抗体预防的感染，在最佳条件下配制的铝佐剂是首选佐剂。由于抗原在铝佐剂上的吸附程度会显著影响免疫原性，因此仔细选择铝佐剂的类型并优化每种抗原的吸附条件非常重要。铝化合物的佐剂作用机制包括在注射部位形成储存库，抗原从该储存库中缓慢释放；通过激活补体、诱导嗜酸性粒细胞增多和激活巨噬细胞来刺激机体的免疫活性细胞；以及由于其颗粒性质和最佳尺寸（<10微米），抗原呈递细胞能够有效摄取铝吸附的抗原颗粒。铝佐剂的局限性包括局部反应、IgE抗体的产生、对某些抗原无效以及无法引发细胞介导的免疫反应，尤其是细胞毒性T细胞反应。磷酸钙具有与铝佐剂相似的佐剂特性，其潜在优势在于它是人体的天然成分且不会增加IgE的产生。需要替代佐剂，特别是对于细胞介导的免疫反应对预防或治疗至关重要的疾病。
