Björling E, Broliden K, Bernardi D, Utter G, Thorstensson R, Chiodi F, Norrby E
Department of Virology, Karolinska Institute, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6082-6. doi: 10.1073/pnas.88.14.6082.
Twenty-five 13- to 35-amino-acid-long peptides representing regions of human immunodeficiency virus type 2 (HIV-2), strain SBL6669, envelope proteins were evaluated for their immunogenic activity in guinea pigs. The peptides were selected to provide homologous representation of sites in the HIV-1 envelope proteins that were previously documented to have a particular immunogenic importance. A number of the HIV-2 peptides were found to be capable of inducing strain SBL6669 neutralizing and antibody-dependent cellular cytotoxicity (ADCC) antibodies. Two overlapping peptides covering amino acids 311-337 representing the central and C-terminal part of the variable third (V3) region, terminology according to Modrow et al. [Modrow, S., Hahn, B., Shaw, G. M., Gallo, R. C., Wong-Staal, F. & Wolf, H. (1987) J. Virol. 61, 570-578], showed the most pronounced capacity to induce neutralizing antibodies. One of the peptides (amino acids 318-337) also induced antibodies mediating ADCC. Two additional regions in the large glycoprotein, gp125, containing linear sites reacting with neutralizing antibodies were identified (amino acids, 119-137 and 472-509). The transmembrane protein, gp36, of HIV-2 harbored two regions of importance for induction of neutralizing antibodies (amino acids 595-614 and 714-729). ADCC activity was induced by two additional gp125-specific peptides (amino acids 291-311 and 446-461). Thus, except for the single V3-specific site there was no correlation between linear immunogenic sites stimulating neutralizing antibody and ADCC activity. These findings pave the way for development of synthetic vaccines against HIV-2 and possibly also simian immunodeficiency virus infections. The capacity of such a product to induce protective immunity can be evaluated in macaque monkeys.
对代表2型人类免疫缺陷病毒（HIV-2）SBL6669株包膜蛋白区域的25种长度为13至35个氨基酸的肽在豚鼠中进行了免疫原活性评估。选择这些肽以提供HIV-1包膜蛋白中先前已证明具有特殊免疫原重要性的位点的同源代表性。发现许多HIV-2肽能够诱导SBL6669株中和抗体和抗体依赖性细胞毒性（ADCC）抗体。根据Modrow等人的术语[Modrow, S., Hahn, B., Shaw, G. M., Gallo, R. C., Wong-Staal, F. & Wolf, H. (1987) J. Virol. 61, 570-578]，覆盖氨基酸311-337的两个重叠肽代表可变第三（V3）区域的中央和C末端部分，显示出诱导中和抗体的最显著能力。其中一个肽（氨基酸318-337）还诱导了介导ADCC的抗体。在大糖蛋白gp125中还鉴定出另外两个与中和抗体反应的线性位点区域（氨基酸119-137和472-509）。HIV-2的跨膜蛋白gp36含有两个对诱导中和抗体很重要的区域（氨基酸595-614和714-729）。另外两个gp125特异性肽（氨基酸291-311和446-461）诱导了ADCC活性。因此，除了单个V3特异性位点外，刺激中和抗体的线性免疫原位点与ADCC活性之间没有相关性。这些发现为开发针对HIV-2以及可能还有猿猴免疫缺陷病毒感染的合成疫苗铺平了道路。可以在猕猴中评估这种产品诱导保护性免疫的能力。
