2026
Enhancement of neutralization potency and breadth by an HIV nanoparticle vaccine containing TLR7/8 agonist 1
Publication Information
Title:Enhancement of neutralization potency and breadth by an HIV nanoparticle vaccine containing TLR7/8 agonist 1
Author(s):Xiaoqian Xin1, Yao Chen1, Haoyue Li, Yunhan Zhang, Mengxue Li, Wei Zhou, Yanfeng Yang, Wei Cao, Jiaping Yu, Wenrong Yao, Yong Liu, Jianxiang Qiu, Qiao Zhang, Zhixin Fang*, Xingyu Jiang*, Feng Gao*
Journal Name, Year, Volume(Issue): Page range:Chemical Engineering Journal, 2026, 535: 175519
DOI:10.1016/j.cej.2026.175519
Abstract:Induction of broad and potent immune responses by vaccines is required to prevent infection from highly variable pathogens like human immunodeficiency viruses (HIV), influenza viruses (IFV) and SARS-CoV-2. The extensive genetic diversity of HIV underscores the need for vaccines capable of eliciting broadly neutralizing antibodies (bnAbs). However, induction of such bnAbs has not been achieved by the current HIV vaccine candidates. To enhance the neutralization breadth, we developed a new vaccine delivery platform consisting of the TLR7/8-activating nanoparticles (TNP) using the microfluidic technology. We then conjugated the native-like HIV-1 envelope (Env) glycoprotein trimers on the TNP surface to generate an HIV nanovaccine (Env_TNP). Env_TNP enhances antigen accumulation in lymph nodes and dendritic cell (DC) activation, increases expression of major histocompatibility complex class II (MHC II) on the DC surface and elicits strong B cell proliferation in mice. Furthermore, immunization in guinea pigs with Env_TNP induces significantly higher titers of neutralizing antibodies (nAbs) and increases the neutralization breadth against diverse HIV-1 strains compared to Env with adjuvant BFA03 or Env alone. These findings demonstrate that the newly developed Env_TNP nanovaccine can enhance the potency and breadth of nAb responses by presenting the Env trimers as large nanoparticles and utilizing the immunostimulatory properties of the TLR7/8 agonist 1 to improve antigen presentation and B cell activation. Overall, this new vaccine delivery platform has strong potentials to improve the immunogenicity of HIV vaccines and can be applied to other protein-based vaccines.
