Liao M, Lu Y, Xiao Y, Dierich M P, Chen Y
Laboratory of Immunology, Research Centre of Medical Science and the School of Life Science and Engineering, Tsinghua University, 100084, Beijing, Peoples Republic of China.
Peptides. 2000 Apr;21(4):463-8. doi: 10.1016/s0196-9781(00)00179-0.
The monoclonal antibody 2F5 recognizing the neutralizing epitope ELDKWA on the C-domain could neutralize 90% of the investigated HIV-1 isolates. Low levels of ELDKWA-epitope-specific antibodies were observed in HIV-1-infected individuals. To induce high levels of antibodies to ELDKW-epitope, C-domain peptide (P2) was conjugated with a carrier peptide (KGGG)(7)-K (K/G). P2-K/G-conjugate induced high level of antibodies in mice by titer 1:25,600 to ELDKWA-epitope. P2-K/G-BSA-conjugate induced antibody response to ELDKWA-epitope (1:320-6400) in mice. The ELDKWA-epitope-specific antibodies of 19.8 and 34.6 microg/per milliliter serum were isolated from two rabbit antiserums (1:25,600). The levels of ELDKWA-epitope-specific antibodies induced in rabbits were greater than 1 microg/ml, a level considered to confer long-term protection. These results demonstrate the potential role of the C-domain peptide of gp41 to develop an effective ELDKWA-based epitope/peptide-vaccine against HIV-1.
识别C结构域上中和表位ELDKWA的单克隆抗体2F5可中和90%的被研究HIV-1分离株。在HIV-1感染个体中观察到低水平的ELDKWA表位特异性抗体。为了诱导产生高水平的针对ELDKW表位的抗体,将C结构域肽(P2)与载体肽(KGGG)(7)-K(K/G)偶联。P2-K/G偶联物在小鼠中诱导产生了效价为1:25,600的针对ELDKWA表位的高水平抗体。P2-K/G-BSA偶联物在小鼠中诱导了针对ELDKWA表位的抗体反应(1:320 - 6400)。从两种兔抗血清(1:25,600)中分离出了每毫升血清中含量分别为19.8和34.6微克的ELDKWA表位特异性抗体。在兔中诱导产生的ELDKWA表位特异性抗体水平高于1微克/毫升,这一水平被认为可提供长期保护。这些结果证明了gp41的C结构域肽在开发一种有效的基于ELDKWA的抗HIV-1表位/肽疫苗方面的潜在作用。