Berkower Ira, Raymond Megan, Muller Jacqueline, Spadaccini Angelo, Aberdeen Anne
Laboratory of Immunoregulation, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics, Bethesda, MD 20892, USA.
Virology. 2004 Mar 30;321(1):75-86. doi: 10.1016/j.virol.2003.12.017.
In order to improve the immunogenicity of HIV-1 envelope glycoproteins, we have fused gp120 to a carrier protein, hepatitis B surface antigen (HBsAg), which is capable of spontaneous assembly into virus-like particles. The HBsAg-gp120 hybrid proteins assembled efficiently into 20-30 nm particles. The particles resemble native HBsAg particles in size and density, consistent with a lipid composition of about 25% and a gp120 content of about 100 per particle. Particulate gp120 folds in its native conformation and is biologically active, as shown by high affinity binding of CD4. The particles express conformational determinants targeted by a panel of broadly cross-reactive neutralizing antibodies, and they show tight packing of gp120. Because the particles are lipoprotein micelles, an array of gp120 on their surface closely mimics gp120 on the surface of HIV-1 virions. These gp120-rich particles can enhance the quality, as well as quantity, of antibodies elicited by a gp120 vaccine.
为了提高HIV-1包膜糖蛋白的免疫原性，我们将gp120与一种载体蛋白——乙肝表面抗原（HBsAg）融合，该抗原能够自发组装成病毒样颗粒。HBsAg-gp120杂合蛋白能高效组装成20 - 30纳米的颗粒。这些颗粒在大小和密度上类似于天然HBsAg颗粒，脂质组成约为25%，每个颗粒的gp120含量约为100，情况与之相符。颗粒状gp120以其天然构象折叠且具有生物活性，如CD4的高亲和力结合所示。这些颗粒表达了一组广泛交叉反应性中和抗体靶向的构象决定簇，并且它们显示出gp120的紧密堆积。由于这些颗粒是脂蛋白微团，其表面的一系列gp120紧密模拟了HIV-1病毒体表面的gp120。这些富含gp120的颗粒能够提高gp120疫苗引发抗体的质量和数量。
