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Published on: February 10, 2022
Chimeric Glycoprotein Nanoparticles Elicit Robust Neutralizing Antibodies Against Epstein-Barr Virus
Cong Sun1, Chu Xie1, Xin-Yan Fang2,3
1State 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.
New chimeric nanoparticles (Chimeric-NPs) effectively induce neutralizing antibodies against Epstein-Barr virus (EBV) fusion proteins. This breakthrough offers promising vaccine strategies for EBV-associated diseases.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Epstein-Barr virus (EBV) is a widespread gammaherpesvirus associated with numerous cancers and autoimmune disorders.
- Current therapeutic and vaccine options for EBV are limited, despite its significant health impact.
- EBV entry into host cells depends on the gB and gHgL glycoproteins, forming the viral fusion apparatus.
Purpose of the Study:
- To design and evaluate chimeric nanoparticles (Chimeric-NPs) that co-display the EBV fusion apparatus.
- To assess the immunogenicity and neutralizing antibody response elicited by Chimeric-NPs compared to traditional vaccine approaches.
- To investigate the B cell response and identify novel neutralizing antibodies against EBV.
Main Methods:
- Development of Chimeric-NPs engineered to co-display EBV gB and gHgL glycoproteins.
- Immunization of mice and nonhuman primates with Chimeric-NPs and assessment of neutralizing antibody titers.
- Analysis of antibody profiles, focusing on targets within the EBV fusion apparatus.
- Single-B cell receptor (BCR) sequencing to characterize the B cell repertoire and identify specific antibody clones.
Main Results:
- Chimeric-NPs induced significantly higher levels of neutralizing antibodies compared to cocktail formulations in both mice and nonhuman primates.
- The antibody response elicited by Chimeric-NPs predominantly targeted the EBV gB glycoprotein, mirroring the natural infection pattern.
- Identification of a novel neutralizing antibody, Fab5, targeting a previously unrecognized vulnerable site on EBV gB.
Conclusions:
- Chimeric-NPs represent a promising vaccine candidate for Epstein-Barr virus, demonstrating superior immunogenicity.
- The study provides insights into the mechanisms of antibody induction by multi-antigen nanoparticle vaccines.
- These findings pave the way for advanced vaccine design strategies against EBV and other pathogens utilizing multi-component fusion apparatuses.
