最近,，猶太大學(xué)(Yeshiva University)醫(yī)學(xué)院的研究人員發(fā)現(xiàn)了兩個(gè)小的蛋白質(zhì)片段，或許有助于科學(xué)家開發(fā)出副作用更小的新型炭疽疫苗,。
炭疽是由炭疽芽孢桿菌引起的一種傳染性疾病,。炭疽桿菌繁殖時(shí)能分泌毒素蛋白，目前針對這種傳染病所使用的疫苗就是利用這些毒素蛋白產(chǎn)生的保護(hù)性抗體,。盡管該疫苗已問世40年,，但它也存在重大缺陷——免疫時(shí)間短，疫苗注射點(diǎn)發(fā)紅,、腫脹或產(chǎn)生嚴(yán)重的過敏反應(yīng),。
在該研究中，研究人員從產(chǎn)生疫苗的毒素蛋白中尋找其中最小的蛋白質(zhì)片段(或稱多肽),，并且這個(gè)小片段的蛋白質(zhì)在注射到動(dòng)物體內(nèi)后,，能引起動(dòng)物產(chǎn)生保護(hù)性抗體。
研究人員將目前使用的疫苗注射到小鼠中,，產(chǎn)生了6種不同的單克隆抗體,，再將疫苗蛋白切斷形成145種多肽，將這些多肽與每種單克隆抗體混合,，從而尋找能被抗體識(shí)別多肽片段,。
最終，研究人員將145個(gè)多肽注射到小鼠后,，找到2個(gè)片段能產(chǎn)生抗體,，并且這些抗體能阻止巨噬細(xì)胞死亡——正常情況下，巨噬細(xì)胞遇到這些炭疽桿菌毒素蛋白則會(huì)發(fā)生死亡,。研究人員下一步打算利用模式動(dòng)物,，研究這些多肽片段是否可以保護(hù)動(dòng)物不受炭疽感染。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
