Chimeric Glycoprotein Nanoparticles Elicit Robust Neutralizing Antibodies Against Epstein–Barr Virus
Abstract
Abstract Epstein‒Barr virus (EBV) is a ubiquitous gammaherpesvirus linked to a broad spectrum of malignancies and autoimmune diseases with no approved therapeutic drugs or vaccines. EBV infection relies on the viral glycoproteins gB and gHgL, which, together, function as the fusion apparatus, mediating viral recognition and membrane fusion in both epithelial and B cells. Despite discovering potent neutralizing antibodies targeting gB and gHgL, the heterogeneous antigen structures and distribution of multiple glycoproteins in the virion hinder rational vaccine design targeting this apparatus complex. In this study, Chimeric nanoparticles (Chimeric‐NPs) are designed that co‐display EBV fusion apparatus and induce significantly more neutralizing antibodies in mice and nonhuman primates than the cocktail counterparts. It is further demonstrated that the Chimeric‐NPs elicited neutralizing antibodies predominantly targeting gB, closely mimicking the antibody induction pattern by the whole EBV virion. Additionally, single‐BCR sequencing is used to analyze the B cell response to Chimeric‐NP, and a novel gB neutralizing antibody Fab5 targeting a new vulnerable site EBV gB is identified. These findings provide novel candidates and vaccine design strategies for EBV and reveal the underlying mechanisms of antibody induction and immune response regulation by chimera vaccines, with potential implications for all multi‐antigen‐harbored pathogens.
Article Details
Authors (16)
Cong Sun
Chu Xie
Xin‐Yan Fang
Cryo‐electron Microscopy Center Department of Biology Southern University of Science and Technology Shenzhen Guangdong 518055 China
Dong‐Chun Hong
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Haoyu Zhang
Pei‐Huang Wu
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Yi‐Na Liu
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Guo‐Long Bu
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
De‐Hai Cao
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Min‐Yi Si‐Tu
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Yong‐Jian Peng
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Jing Wang
Hunan Cancer Hospital Changsha China
Guo‐Kai Feng
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China
Qian Zhong
Zheng Liu
Mu‐Sheng Zeng
State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangdong 510060 China