Design of hepadnavirus core protein-based chimeric virus-like particles carrying epitopes from respiratory syncytial virus

作者：Shuai Shao, Xuefeng Zhang, Jun Hou, Sen Yang, Zi Bo Han, Hai Lan Wu, Fang Tang, Xin Yu Li, Ze Hua Lei, Zi Xin Zhao, Shu Xiang Li, Zhao Ming Liu, Pu Shan, Yu Jin, Ji Guo Su, Liang Yu, Jing Zhang, Qi Ming Li · 发表于：npj Vaccines · 年份：2024 · DOI：10.1038/s41541-024-00855-7 · 被引用次数：4 · 研究领域：Respiratory viral infections research、Viral gastroenteritis research and epidemiology、Viral Infections and Outbreaks Research

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an "epitope-focused" vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for...