title: Recent Progress toward Engineering HIV-1-Specific Neutralizing Monoclonal Antibodies.
abstract: The recent discoveries of broadly potent neutralizing human monoclonal antibodies represent a new generation of antiretrovirals for the treatment and prophylaxis. Antibodies are generally considered more effective and safer and have been proved to provide passive protection against mucosal challenge in humanized mice and macaques. Several neutralizing Abs could protect animals against HIV-1 but are not effective when used in an established infected model for therapy. In order to overcome the limitation of antiviral activities, multiple antibody-engineering technologies have been explored to generate "the better" neutralizing antibodies against HIV-1 since bNAbs attack viral entry by various mechanisms. Thus, a promising direction of research is to discover and exploit rational antibody combination or engineered antibodies (eAbs) as potential candidate therapeutics against HIV-1. It has been reported that inclusion of fusion-neutralizing antibodies in a set of bNAbs could improve their overall activities and neutralizing spectrum. Here, we review several routes for engineering bNAbs, such as design and generation of bispecific antibodies, specific glycosylation of antibodies to enhance antiviral activity, and variable region-specific modification guided by structure and computer, as well as reviewing antibody-delivery technologies by non-viral vector, viral vector, and human hematopoietic stem/progenitor cells transduced with a lentiviral construct. We also discuss the optimized antiviral activities and benefits of these strategy and potential mechanisms.
authors.affiliation: Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Sciences , Kunming , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University , Tianjin , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Sciences , Kunming , China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zheng
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, China; School of Medicine, Nankai University, Tianjin, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
keywords: HIV-1 neutralizing antibodies; antibody engineering; antigen binding; bispecific antibody; gene delivery; variable region