Recently，Journal of Virology online reported a seminal work on development HIV-1 virus like particles (VLP) using stably transfected Drosophila S2 cells by Professor Paul Zhou’s laboratory at the Institut Pasteur of Shanghai, Chinese Academy of Sciences.
Although a recent phase III studyon RV144 conducted in Thailand have created optimism in the field of HIV vaccine development, an optimal vaccine still requires a component that elicits both broadly neutralizing antibody and memory T cell responses. HIV-1 VLP, because they display authentic envelope spikes on the particle surface, may be developed into such immunogens. However, in one way or the other current systems for HIV-1 VLP production have many limitations. To overcome these, Ph.D. students YANG Lifei, SONG Yufeng and others in Professor Paul Zhou’s laboratory developed a novel strategy to produce HIV-1 VLP using stably transfected Drosophila S2 cells. They demonstrated that HIV-1 envelope proteins are properly cleaved, glycosylated, and incorporated into VLP with Gag. The amount of VLP released into culture supernatants is comparable to those produced by insect cells infected with recombinant baculoviruses. Moreover, cryo-electron microscopy tomography revealed average 17 spikes per purified VLP, and antigenic epitopes on the spikes were recognized by the broadly neutralizing antibodies 2G12, b12, VRC01, and 4E10. Finally, mice primed with DNA and boosted with VLP in the presence of CpG exhibited anti-envelope antibody responses, including ELISA binding, neutralizing, antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated viral inhibition, as well as envelope and Gag-specific CD8 T cell responses. Thus, they conclude that HIV-1 VLP produced by the S2 expression system has many desirable features to be developed into a vaccine component against HIV-1.
This work was done in the collaboration with Professor ZHU Ping’s laboratory at the Institute of Biophysics, Chinese academy of Sciences and supported by research grants from the National Science and Technology Major Project of the Ministry of Science and Technology of China.
HIV-1 VLP revealed by Cryo-EM Tomography. Red arrows indicate HIV-1 spikes.