Dolimbek Behzod Z, Jankovic Joseph, Atassi M Zouhair
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.
Immunol Invest. 2002 Aug-Nov;31(3-4):247-62. doi: 10.1081/imm-120016244.
The present studies were carried out in order to investigate the cross-reaction of botulinum neurotoxins (BoNTs) with human and mouse antibodies against tetanus neurotoxin (TeNT) and determine whether injection of BoNT into a host that has been primed with TeNT would result in boosting of the response to the injected BoNT. Human antisera against TeNT obtained from 9 individuals were found to exhibit substantial cross-reaction with BoNTs A and B. We prepared antibodies (Abs) against inactivated tetanus neurotoxin (TeNT) in outbred mice and determined the binding of these Abs to active TeNT and active botulinum neurotoxins (BoNTs) A and B. Blood samples were collected before immunization (day 0) and on days 42, 82 and 125 after the first injection. The reactions of these sera with the immunizing antigen (inactivated TeNT), active TeNT, active BoNT/A and active BoNT/B were determined. At a fixed dilution (1:62.5 v/v), the sera contained high levels of Abs that reacted with TeNT and also with BoNTs A and B. Throughout the test period (up through day 125) and at different dilutions the cross-reactions of the antisera with BoNT/B were almost twice those with BoNT/A. The reactions of the antisera with the immunizing antigen (inactive TeNT) or with active TeNT were essentially equal throughout the dilution range tested (1:16-1:500 v/v). To determine whether injection of BoNT/A or B into a host that had been primed with TeNT resulted in boosting of the response to the priming antigen (TeNT) as well as BoNT/A or B, mice were primed with TeNT and boosted 21 days later with TeNT, BoNT/A or BoNT/B. Appropriate controls were also employed. Blood samples were collected prior to TeNT priming (day -1) and on days 21, 32, 46 and 67 after priming. In TeNT-primed mice, BoNTs A or B boosted the anti-TeNT Ab responses slightly but had no significant boosting effect on the Ab populations that bind to BoNTs A or B. It is concluded that while Abs against TeNT cross react with BoNTs and the cross reaction with BoNT/B is almost double that of BoNT/A, injection of BoNTs A or B in the presence of a prior active immunity against TeNT is not very likely to make the host mount an Ab response against the injected BoNT.
开展本研究是为了调查肉毒杆菌神经毒素（BoNTs）与人及小鼠抗破伤风神经毒素（TeNT）抗体的交叉反应，并确定向已用TeNT致敏的宿主体内注射BoNT是否会增强对注射的BoNT的反应。发现从9名个体获得的抗TeNT人抗血清与BoNTs A和B表现出显著的交叉反应。我们在远交系小鼠中制备了抗灭活破伤风神经毒素（TeNT）的抗体（Abs），并确定了这些Abs与活性TeNT以及活性肉毒杆菌神经毒素（BoNTs）A和B的结合情况。在免疫前（第0天）以及首次注射后第42、82和125天采集血样。测定了这些血清与免疫抗原（灭活TeNT）、活性TeNT、活性BoNT/A和活性BoNT/B的反应。在固定稀释度（1:62.5 v/v）下，血清中含有高水平的与TeNT反应且也与BoNTs A和B反应的Abs。在整个测试期（直至第125天）以及不同稀释度下，抗血清与BoNT/B的交叉反应几乎是与BoNT/A交叉反应的两倍。在测试的整个稀释范围内（1:16 - 1:500 v/v），抗血清与免疫抗原（无活性TeNT）或活性TeNT的反应基本相同。为了确定向已用TeNT致敏的宿主体内注射BoNT/A或B是否会增强对致敏抗原（TeNT）以及BoNT/A或B的反应，用TeNT对小鼠进行致敏，并在21天后用TeNT、BoNT/A或BoNT/B进行加强免疫。还采用了适当的对照。在TeNT致敏前（第 -1天）以及致敏后第21、32、46和67天采集血样。在TeNT致敏的小鼠中，BoNTs A或B略微增强了抗TeNT抗体反应，但对与BoNTs A或B结合的抗体群体没有显著的增强作用。得出的结论是，虽然抗TeNT的Abs与BoNTs发生交叉反应，且与BoNT/B的交叉反应几乎是与BoNT/A交叉反应的两倍，但在先前存在针对TeNT的主动免疫的情况下注射BoNTs A或B不太可能使宿主对注射的BoNT产生抗体反应。
