Ma J, Bulger P A, Davis D R, Perilli-Palmer B, Bedore D A, Kensil C R, Young E M, Hung C H, Seals J R, Pavia C S
Cambridge Biotech Corporation, Worcester, MA 01605.
Vaccine. 1994 Aug;12(10):925-32. doi: 10.1016/0264-410x(94)90036-1.
The impact of the adjuvants QS-21 and aluminium hydroxide (alum) on the immunogenicity of recombinant outer surface proteins A (OspA) and B (OspB) of Borrelia burgdorferi was investigated. Both non-acylated OspA and OspB derived from strain B31 were expressed in Escherichia coli and purified by reversible citraconylation and anion-exchange chromatography. Antisera to OspA or OspB were prepared in mice with antigens formulated with QS-21 or alum, and evaluated for specific immunoglobulin G isotypes, agglutination and borreliacidal activity. QS-21 significantly enhanced IgG2a and IgG2b antibody responses to OspA and OspB, and IgG1 response to OspA when compared with the formulation containing antigen alone. In contrast, alum significantly inhibited the induction of IgG2a and IgG2b responses to OspA. Alum had no significant effect on IgG1 response to OspA, or IgG2a and IgG2b responses to OspB, but significantly enhanced IgG1 antibody response to OspB. Antisera to OspA or OspB formulated by QS-21 possessed higher titres of agglutinating antibody than antisera to OspA or OspB alone. Borreliacidal activity was eight- to 64-fold higher in antisera to OspA formulated with QS-21 than in antisera to OspA formulated with or without alum. These antisera were highly borreliacidal to New York strain B31, a California isolate CA-2-87, German isolate Fr, and Swedish isolate G25. Antisera to OspB formulated with QS-21 were highly borreliacidal to strains B31 and Fr, but not to CA-2-87 and G25. Antisera to OspB formulated with alum were borreliacidal only to B31. Thus, OspA was superior to OspB and QS-21 superior to alum at eliciting functional antibody responses.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了佐剂QS-21和氢氧化铝（明矾）对伯氏疏螺旋体重组外表面蛋白A（OspA）和B（OspB）免疫原性的影响。从B31菌株衍生的非酰化OspA和OspB均在大肠杆菌中表达，并通过可逆柠康酰化和阴离子交换色谱法进行纯化。用含有QS-21或明矾的抗原在小鼠中制备抗OspA或OspB血清，并评估其特异性免疫球蛋白G亚型、凝集和杀螺旋体活性。与仅含抗原的制剂相比，QS-21显著增强了对OspA和OspB的IgG2a和IgG2b抗体反应，以及对OspA的IgG1反应。相比之下，明矾显著抑制了对OspA的IgG2a和IgG2b反应的诱导。明矾对OspA的IgG1反应或对OspB的IgG2a和IgG2b反应没有显著影响，但显著增强了对OspB的IgG1抗体反应。由QS-21配制的抗OspA或OspB血清比单独的抗OspA或OspB血清具有更高滴度的凝集抗体。用QS-21配制的抗OspA血清的杀螺旋体活性比用明矾配制或未用明矾配制的抗OspA血清高8至64倍。这些血清对纽约菌株B31、加利福尼亚分离株CA-2-87、德国分离株Fr和瑞典分离株G25具有高度杀螺旋体活性。用QS-21配制的抗OspB血清对菌株B31和Fr具有高度杀螺旋体活性，但对CA-2-87和G25没有。用明矾配制的抗OspB血清仅对B31具有杀螺旋体活性。因此，在引发功能性抗体反应方面，OspA优于OspB，QS-21优于明矾。（摘要截短于250字）
