最近，犹太大学(Yeshiva University)医学院的研究人员发现了两个小的蛋白质片段，或许有助于科学家开发出副作用更小的新型炭疽疫苗。
炭疽是由炭疽芽孢杆菌引起的一种传染性疾病。炭疽杆菌繁殖时能分泌毒素蛋白，目前针对这种传染病所使用的疫苗就是利用这些毒素蛋白产生的保护性抗体。尽管该疫苗已问世40年，但它也存在重大缺陷——免疫时间短，疫苗注射点发红、肿胀或产生严重的过敏反应。
在该研究中，研究人员从产生疫苗的毒素蛋白中寻找其中最小的蛋白质片段(或称多肽)，并且这个小片段的蛋白质在注射到动物体内后，能引起动物产生保护性抗体。
研究人员将目前使用的疫苗注射到小鼠中，产生了6种不同的单克隆抗体，再将疫苗蛋白切断形成145种多肽，将这些多肽与每种单克隆抗体混合，从而寻找能被抗体识别多肽片段。
最终，研究人员将145个多肽注射到小鼠后，找到2个片段能产生抗体，并且这些抗体能阻止巨噬细胞死亡——正常情况下，巨噬细胞遇到这些炭疽杆菌毒素蛋白则会发生死亡。研究人员下一步打算利用模式动物，研究这些多肽片段是否可以保护动物不受炭疽感染。（生物谷Bioon.com）
生物谷推荐原始出处：
J. Biol. Chem., Vol. 284, Issue 37, 25077-25086, September 11, 2009
Identification of Linear Epitopes in Bacillus anthracis Protective Antigen Bound by Neutralizing Antibodies*
Nareen Abboud, Magdia De Jesus, Antonio Nakouzi, Radames J. B. Cordero, Mario Pujato, András Fiser, Johanna Rivera1, and Arturo Casadevall?12
From the From the Department of Microbiology and Immunology, , ?Department of Medicine, Division of Infectious Diseases, and , Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461
ABSTRACT
Protective antigen (PA), the binding subunit of anthrax toxin, is the major component in the current anthrax vaccine, but the fine antigenic structure of PA is not well defined. To identify linear neutralizing epitopes of PA, 145 overlapping peptides covering the entire sequence of the protein were synthesized. Six monoclonal antibodies (mAbs) and antisera from mice specific for PA were tested for their reactivity to the peptides by enzyme-linked immunosorbent assays. Three major linear immunodominant B-cell epitopes were mapped to residues Leu156 to Ser170, Val196 to Ile210, and Ser312 to Asn326 of the PA protein. Two mAbs with toxin-neutralizing activity recognized two different epitopes in close proximity to the furin cleavage site in domain 1. The three-dimensional complex structure of PA and its neutralizing mAbs 7.5G and 19D9 were modeled using the molecular docking method providing models for the interacting epitope and paratope residues. For both mAbs, LeTx neutralization was associated with interference with furin cleavage, but they differed in effectiveness depending on whether they bound on the N- or C-terminal aspect of the cleaved products. The two peptides containing these epitopes that include amino acids Leu156–Ser170 and Val196–Ile210 were immunogenic and elicited neutralizing antibody responses to PA. These results identify the first linear neutralizing epitopes of PA and show that peptides containing epitope sequences can elicit neutralizing antibody responses, a finding that could be exploited for vaccine design.
