Hu Zhulong, Tian Siyu, Zhou Yu, Wang Yanqun, Li Yu, Zhang Senyan, Wei Peilan, Zhuang Zhen, Ren Luo, Liu Jiao, Zang Na, Yu Rui, Ding Yanbin, Guo Yan, Jing Cai, Chen Hang, Zhang Caixia, Yao Yuanfeng, Deng Chunping, Wei Rui, Zhou Peng, Zou Yongjuan, Zhao Dawei, Liu Shuyun, Fu Meijuan, Mo Xuejun, Peng Guodong, Liu Enmei, Zhao Jincun, Li Yuanyuan, Jin Jing
Patronus Biotech Co. Ltd., Guangzhou, China.
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, China.
J Virol. 2025 Aug 26:e0090325. doi: 10.1128/jvi.00903-25.
Respiratory syncytial virus (RSV) is a global public health concern. Currently, RSV vaccines are approved only for use in older adults, while preventing the disease in infants and children, as well as ensuring vaccine durability, remains a significant challenge. The pre-fusion conformation of the RSV fusion (F) glycoprotein is a primary target for vaccine development, as it elicits significantly higher neutralizing antibody titers than the post-fusion form. Here, we conjugated either the first-generation RSV pre-fusion F antigen, DS-Cav1, or the second-generation antigen, Sc9-10, to a computationally designed nanoparticle platform, NPM, via a Catcher/Tag system. Conjugating RSV pre-fusion F to NPM significantly enhanced immunogenicity, stability, and bioactivity compared to display on the I53-50 nanoparticle platform. In a cotton rat challenge model, Sc9-10-NPM vaccine candidates provided effective protection across a wide dosage range, regardless of the adjuvant used. These results support the continued development of this promising nanoparticle-based RSV vaccine candidate.IMPORTANCERespiratory syncytial virus (RSV) is a major cause of severe respiratory illness in infants and young children worldwide, yet few vaccines are approved for use in these vulnerable groups. In this study, we developed a new vaccine candidate based on a second-generation RSV pre-fusion F protein, engineered for improved stability and immune response. This protein was displayed on a specially designed nanoparticle platform to enhance its effectiveness and durability. The vaccine elicited strong immune responses and provided complete protection in preclinical models, even without the use of potent adjuvants that may cause side effects. Importantly, it did not trigger adverse vaccine-enhanced disease (VED). These findings suggest that this vaccine design could offer a safer and more effective way to protect infants and other at-risk populations from RSV. Additionally, the nanoparticle platform may be applicable to vaccines against other infectious diseases.
呼吸道合胞病毒（RSV）是一个全球公共卫生问题。目前，RSV疫苗仅被批准用于老年人，而在婴儿和儿童中预防该疾病以及确保疫苗的持久性仍然是一项重大挑战。RSV融合（F）糖蛋白的预融合构象是疫苗开发的主要靶点，因为它引发的中和抗体滴度比融合后形式高得多。在此，我们通过捕获器/标签系统将第一代RSV预融合F抗原DS-Cav1或第二代抗原Sc9-10与经计算设计的纳米颗粒平台NPM偶联。与展示在I53-50纳米颗粒平台上相比，将RSV预融合F与NPM偶联显著增强了免疫原性、稳定性和生物活性。在棉鼠攻毒模型中，Sc9-10-NPM候选疫苗在广泛的剂量范围内都能提供有效的保护，无论使用何种佐剂。这些结果支持继续开发这种有前景的基于纳米颗粒的RSV候选疫苗。
重要性
呼吸道合胞病毒（RSV）是全球婴幼儿严重呼吸道疾病的主要病因，但很少有疫苗被批准用于这些弱势群体。在本研究中，我们基于第二代RSV预融合F蛋白开发了一种新的候选疫苗，该蛋白经过工程改造以提高稳定性和免疫反应。这种蛋白展示在一个经过特殊设计的纳米颗粒平台上，以增强其有效性和持久性。该疫苗引发了强烈的免疫反应，并在临床前模型中提供了完全保护，即使不使用可能引起副作用的强效佐剂。重要的是，它不会引发不良的疫苗增强疾病（VED）。这些发现表明，这种疫苗设计可能提供一种更安全、更有效的方法来保护婴儿和其他高危人群免受RSV感染。此外，该纳米颗粒平台可能适用于针对其他传染病的疫苗。
