Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax.
Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax.
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重组保护性抗原的免疫原性和对抗炭疽气溶胶攻击的功效。
DOI：
10.1128/iai.73.9.5978-5987.2005
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发表时间：
2005
影响因子：
3.1
通讯作者：
Quinn,CP
中科院分区：
文献类型：
--
作者：
Williamson,ED;Hodgson,I;Walker,NJ;Topping,AW;Duchars,MG;Mott,JM;Estep,J;Lebutt,C;Flick-Smith,HC;Jones,HE;Li,H;Quinn,CP
用重组炭疽芽孢杆菌保护性抗原(RPA)免疫恒河猴。用25μg或更多的OFB免疫恒河猴。与接受英国现有许可疫苗(炭疽疫苗沉淀[AVP])的猕猴相比，与接受Alwater Gel结合的枯草杆菌表达的RPA的猕猴相比，RPA对RPA的免疫球蛋白G(IgG)反应显著增强，尽管同型图谱没有变化，但偏向于IgG1和IgG2亚类。所有免疫组的免疫猕猴血清均含有毒素中和抗体，可识别PA的所有结构域。用现有疫苗(AVP和美国疫苗炭疽疫苗吸附)免疫的猕猴主要识别PA的N末端(结构域1到3)，而用RPA免疫的猕猴识别PA的N末端和C末端结构域。猕猴免疫后产生的抗血清可在体外保护巨噬细胞免受致死毒素的细胞毒作用。将免疫猕猴血清中提纯的免疫球蛋白G被动转移到幼龄A/J小鼠体内，可保护小鼠免受B组的攻击。炭疽以剂量相关的方式。被动转移500μg猕猴免疫球蛋白的保护力与供体猕猴中和抗体效价显著相关(P=0.003；r=0.4)。随后，一组单独的恒河猴免疫了50μg的大肠杆菌来源的RPA吸附到Alwater Gel上，对目标剂量200 50%致死剂量的雾化B完全保护。炭疽病。这些数据为RPA免疫猕猴中存在预防炭疽感染的免疫相关因素提供了一些初步证据。
Immunization with a recombinant form of the protective antigen (rPA) fromBacillus anthracishas been carried out with rhesus macaques. Rhesus macaques immunized with 25 μg or more ofB. subtilis-expressed rPA bound to alhydrogel had a significantly increased immunoglobulin G (IgG) response to rPA compared with macaques receiving the existing licensed vaccine from the United Kingdom (anthrax vaccine precipitated [AVP]), although the isotype profile was unchanged, with bias towards the IgG1 and IgG2 subclasses. Immune macaque sera from all immunized groups contained toxin-neutralizing antibody and recognized all the domains of PA. While the recognition of the N terminus of PA (domains 1 to 3) was predominant in macaques immunized with the existing vaccines (AVP and the U.S. vaccine anthrax vaccine adsorbed), macaques immunized with rPA recognized the N- and C-terminal domains of PA. Antiserum derived from immunized macaques protected macrophages in vitro against the cytotoxic effects of lethal toxin. Passive transfer of IgG purified from immune macaque serum into naive A/J mice conferred protection against challenge withB. anthracisin a dose-related manner. The protection conferred by passive transfer of 500 μg macaque IgG correlated significantly (P= 0.003;r= 0.4) with the titers of neutralizing antibody in donor macaques. Subsequently, a separate group of rhesus macaques immunized with 50 μg ofEscherichia coli-derived rPA adsorbed to alhydrogel was fully protected against a target dose of 200 50% lethal doses of aerosolizedB. anthracis. These data provide some preliminary evidence for the existence of immune correlates of protection against anthrax infection in rhesus macaques immunized with rPA.