Vaccination with nanoparticles displaying gH/gL from Epstein-Barr virus elicits limited cross-protection against rhesus lymphocryptovirus

• Published in: Cell reports. Medicine 2024-06, Vol.5 (6), p.101587, Article 101587
• Main Authors: Edwards, Kristina R., Schmidt, Karina, Homad, Leah J., Kher, Gargi M., Xu, Guoyue, Rodrigues, Kristen A., Ben-Akiva, Elana, Abbott, Joe, Prlic, Martin, Newell, Evan W., De Rosa, Stephen C., Irvine, Darrell J., Pancera, Marie, McGuire, Andrew T.
• Format: Article
• Language: English
• Subjects: adjuvants; Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; challenge studies; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - prevention & control; Epstein-Barr Virus Infections - virology; Herpesviridae Infections - immunology; Herpesviridae Infections - prevention & control; Herpesviridae Infections - virology; Herpesvirus 4, Human - immunology; Humans; Lymphocryptovirus - immunology; Macaca mulatta; nanoparticles; Nanoparticles - chemistry; neutralizing antibodies; rhesus lymphocryptovirus; Vaccination - methods; vaccines; Viral Vaccines - administration & dosage; Viral Vaccines - immunology
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2024.101587

Epstein-Barr virus (EBV) is associated with infectious mononucleosis, cancer, and multiple sclerosis. A vaccine that prevents infection and/or EBV-associated morbidity is an unmet need. The viral gH/gL glycoprotein complex is essential for infectivity, making it an attractive vaccine target. Here, we evaluate the immunogenicity of a gH/gL nanoparticle vaccine adjuvanted with the Sigma Adjuvant System (SAS) or a saponin/monophosphoryl lipid A nanoparticle (SMNP) in rhesus macaques. Formulation with SMNP elicits higher titers of neutralizing antibodies and more vaccine-specific CD4+ T cells. All but one animal in the SMNP group were infected after oral challenge with the EBV ortholog rhesus lymphocryptovirus (rhLCV). Their immune plasma had a 10- to 100-fold lower reactivity against rhLCV gH/gL compared to EBV gH/gL. Anti-EBV neutralizing monoclonal antibodies showed reduced binding to rhLCV gH/gL, demonstrating that EBV gH/gL neutralizing epitopes are poorly conserved on rhLCV gH/gL. Prevention of rhLCV infection despite antigenic disparity supports clinical development of gH/gL nanoparticle vaccines against EBV. [Display omitted] •Macaques were immunized with EBV gH/gL nanoparticles formulated with two adjuvants•Animals were challenged with rhesus lymphocryptovirus, the EBV ortholog infecting macaques•One adjuvant was more immunogenic, affording some protection from rhLCV challenge•Antibodies elicited by the EBV vaccine were poorly matched to the rhLCV challenge virus EBV is a cancer-associated pathogen for which there is no vaccine. Here, Edwards et al. demonstrate that a vaccine comprising nanoparticles displaying the EBV gH/gL glycoprotein complex provides partial protection against experimental infection of rhesus macaques. These results support the use of gH/gL nanoparticles for EBV vaccine development.