Weissburg R P, Berman P W, Cleland J L, Eastman D, Farina F, Frie S, Lim A, Mordenti J, Nguyen T T, Peterson M R
Pharmaceutical R&D, Genentech, Inc, South San Francisco, California 94080, USA.
Pharm Res. 1995 Oct;12(10):1439-46. doi: 10.1023/a:1016266916893.
The characterization of recombinant MN gp120/alum vaccine requires the study of the gp120-alum interaction for the successful formulation of an alum-based HIV-1 vaccine.
Several observations suggest that the gp120-alum interaction is weak, wherein buffer counterions such as phosphate, sulfate, bicarbonate may cause the desorption of gp120 from alum. Comparison of gp120 with other proteins using particle mobility measurements shows that the weak binding of gp120 to alum is not an anomaly. Serum and plasma also cause desorption of gp120 from alum with a half-life of only a few minutes, wherein this half-life may be faster than the in-vivo recruitment of antigen presenting cells to the site of immunization.
Immunization of guinea pigs, rabbits and baboons with gp120 formulated in alum or saline demonstrated that alum provides adjuvant activity for gp120, particularly after early immunizations, but the adjuvant effect is attenuated after several boosts.
These observations indicate that both the antigen and the adjuvant require optimization together.
重组MN gp120/明矾疫苗的特性研究需要对gp120与明矾的相互作用进行研究，以便成功制备基于明矾的HIV-1疫苗。
多项观察结果表明，gp120与明矾的相互作用较弱，其中缓冲液中的抗衡离子如磷酸盐、硫酸盐、碳酸氢盐可能导致gp120从明矾上解吸。通过颗粒迁移率测量比较gp120与其他蛋白质，结果表明gp120与明矾的弱结合并非异常现象。血清和血浆也会导致gp120从明矾上解吸，半衰期仅为几分钟，其中这个半衰期可能比体内抗原呈递细胞募集到免疫部位的速度还要快。
用明矾或盐水中配制的gp120免疫豚鼠、兔子和狒狒，结果表明明矾为gp120提供佐剂活性，尤其是在早期免疫后，但在多次加强免疫后佐剂效果会减弱。
这些观察结果表明，抗原和佐剂都需要一起优化。
