Silvera P, Flanagan B, Kent K, Rud E, Powell C, Corcoran T, Bruck C, Thiriart C, Haigwood N L, Stott E J
National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom.
AIDS Res Hum Retroviruses. 1994 Oct;10(10):1295-304. doi: 10.1089/aid.1994.10.1295.
To characterize the serological response to SIV envelope, induced by vaccination with different envelope immunogens or by SIV infection, plasma samples from 11 cynomolgus macaques infected with simian immunodeficiency virus (SIV) and from 16 macaques vaccinated with three different recombinant envelope proteins were analyzed by (1) ELISA, using a variety of antigens including overlapping peptides encompassing the entire sequence of the envelope protein of SIV, and (2) competition assays, using neutralizing monoclonal antibodies to SIV gp120. Seven regions of SIV envelope were predicted to be antigenic. Peptides representing four of these, in the second and third variable regions (V2 and V3) and the fourth constant (C4) region of gp120 and the Gnann region of gp41, were recognized by the majority of sera from infected and vaccinated animals. Additional antigenic regions were identified in the first and fourth variable domains (V1 and V4) and the carboxy terminus (C5) of gp120 and in three additional regions of gp41. Most infected and vaccinated animals made antibodies that competed with the binding of the three conformational MAbs. Among the vaccinated groups, antibodies induced by vaccination with precursor glycoproteins (gp140 or gp160) recognized several additional gp120 epitopes when compared with antibodies induced by external glycoprotein gp130. Sera from infected animals showed a more restricted gp120 response (17 of 46 peptides recognized) compared to animals vaccinated with precursor glycoproteins (31 peptides recognized). The converse was true for antibodies to gp41. Sera from animals vaccinated with recombinant gp140, produced in insect cells, were the only group that failed to compete with the binding of conformational MAbs. Finally, the development of antibodies to specific epitopes of gp120 and gp41 revealed differences between long-term survivors and nonsurvivors, implying that responses to specific epitopes may be important in conferring resistance to disease progression.
为了描述接种不同包膜免疫原或感染猴免疫缺陷病毒（SIV）所诱导的针对SIV包膜的血清学反应，对11只感染了SIV的食蟹猴和16只接种了三种不同重组包膜蛋白的猕猴的血浆样本进行了分析，分析方法如下：（1）酶联免疫吸附测定（ELISA），使用多种抗原，包括涵盖SIV包膜蛋白全序列的重叠肽；（2）竞争试验，使用针对SIV gp120的中和单克隆抗体。预测SIV包膜有七个区域具有抗原性。代表其中四个区域的肽，即gp120的第二和第三可变区（V2和V3）、第四恒定区（C4）以及gp41的Gnann区，被大多数感染和接种动物的血清所识别。在gp120的第一和第四可变域（V1和V4）以及羧基末端（C5）和gp41的另外三个区域中鉴定出了额外的抗原区域。大多数感染和接种动物产生的抗体与三种构象单克隆抗体的结合存在竞争。在接种组中，与外膜糖蛋白gp130诱导的抗体相比，接种前体糖蛋白（gp140或gp160）诱导的抗体识别出了几个额外的gp120表位。与接种前体糖蛋白的动物（识别31个肽）相比，感染动物的血清对gp120的反应更受限制（识别46个肽中的17个）。针对gp41的抗体情况则相反。在昆虫细胞中产生的重组gp140接种动物的血清是唯一一组不能与构象单克隆抗体的结合产生竞争的血清。最后，针对gp120和gp41特定表位的抗体的产生揭示了长期存活者和非存活者之间的差异，这意味着对特定表位的反应可能对赋予疾病进展抗性很重要。
