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

Kristina R Edwards; Karina Schmidt; Leah J Homad; Gargi M Kher; Guoyue Xu; Kristen A Rodrigues; Elana Ben-Akiva; Joe Abbott; Martin Prlic; Evan W Newell; Stephen C De Rosa; Darrell J Irvine; Marie Pancera; Andrew T McGuire

doi:10.1016/j.xcrm.2024.101587

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

Cell Rep Med. 2024 Jun 18;5(6):101587. doi: 10.1016/j.xcrm.2024.101587. Epub 2024 May 22.

Authors

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
² Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA.
⁴ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA; Departments of Biological Engineering and Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Department of Immunology, University of Washington, Seattle, WA, USA.
⁶ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
⁷ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA; Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
⁸ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA. Electronic address: [email protected].

Abstract

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.

Keywords: Epstein-Barr virus; adjuvants; challenge studies; nanoparticles; neutralizing antibodies; rhesus lymphocryptovirus; vaccines.

MeSH terms

Adjuvants, Immunologic / administration & dosage
Adjuvants, Immunologic / pharmacology
Animals
Antibodies, Neutralizing* / immunology
Antibodies, Viral / immunology
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* / chemistry
Vaccination* / methods
Viral Vaccines / administration & dosage
Viral Vaccines / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Viral Vaccines
Adjuvants, Immunologic

Grants and funding

R01 CA264646/CA/NCI NIH HHS/United States