State Key Laboratory for Infectious Diseases Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China.
Retrovirology. 2010 Sep 1;7:71. doi: 10.1186/1742-4690-7-71.
In order to induce a potent and cross-reactive neutralizing antibody (nAb), an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV). The Chinese equine infectious anemia virus (EIAV) attenuated vaccine has controlled the epidemic of this virus after its vaccination in over 70 million equine animals during the last 3 decades in China. Data from our past studies demonstrate that the Env protein of this vaccine plays a pivotal role in protecting horses from both homologous and heterogeneous EIAV challenges. Therefore, the amino acid sequence information from the Chinese EIAV attenuated vaccine, in comparison with the parental wild-type EIAV strains, was applied to modify the corresponding region of the envelope glycoprotein of HIV-1 CN54. The direction of the mutations was made towards the amino acids conserved in the two EIAV vaccine strains, distinguishing them from the two wild-type strains. The purpose of the modification was to enhance the immunogenicity of the HIV Env.
The induced nAb by the modified HIV Env neutralized HIV-1 B and B'/C viruses at the highest titer of 1:270. Further studies showed that a single amino acid change in the C1 region accounts for the substantial enhancement in induction of anti-HIV-1 neutralizing antibodies.
This study shows that an HIV envelope modified by the information of another lentivirus vaccine induces effective broadly neutralizing antibodies. A single amino acid mutation was found to increase the immunogenicity of the HIV Env.
为了诱导有效的、具有交叉反应性的中和抗体（nAb），对于包括人类免疫缺陷病毒（HIV）疫苗在内的许多病毒疫苗而言，有效的包膜免疫原至关重要。中国马传染性贫血病毒（EIAV）弱毒疫苗在过去 30 年中在中国为超过 7000 万匹马接种，已控制了该病毒的流行。我们过去的研究数据表明，该疫苗的Env 蛋白在保护马免受同源和异源 EIAV 挑战方面发挥着关键作用。因此，与亲本野生型 EIAV 株相比，中国 EIAV 弱毒疫苗的氨基酸序列信息被应用于修饰 HIV-1 CN54 包膜糖蛋白的相应区域。突变的方向是针对两种 EIAV 疫苗株中保守的氨基酸，使它们与两种野生型株区分开来。修饰的目的是增强 HIV Env 的免疫原性。
修饰后的 HIV Env 诱导的 nAb 对 HIV-1 B 和 B'/C 病毒的中和效价最高达 1:270。进一步的研究表明，C1 区的单个氨基酸变化导致诱导抗 HIV-1 中和抗体的能力显著增强。
本研究表明，一种由另一种慢病毒疫苗信息修饰的 HIV 包膜可诱导有效的广谱中和抗体。发现单个氨基酸突变可提高 HIV Env 的免疫原性。
