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Evaluation of HSV-2 gE Binding to IgG-Fc and Application for Vaccine Development.
Galli, Jennifer D; Horton, Melanie; Durr, Eberhard; Heidecker, Gwendolyn J; Freed, Daniel; Fridman, Arthur; Wang, Dai; Zhang, Lan.
Afiliación
  • Galli JD; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
  • Horton M; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
  • Durr E; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
  • Heidecker GJ; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
  • Freed D; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
  • Fridman A; Data Science and Scientific Informatics, Merck & Co., Inc., Rahway, NJ 07065, USA.
  • Wang D; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
  • Zhang L; Infectious Diseases and Vaccines Discovery, Merck & Co., Inc., West Point, PA 19486, USA.
Vaccines (Basel) ; 10(2)2022 Jan 25.
Article en En | MEDLINE | ID: mdl-35214644
Glycoprotein E (gE) and glycoprotein I (gI) are expressed as a heterodimer on the surface of Herpes simplex virus (HSV). Glycoprotein E binds Fc domain of immunoglobulin G (IgG) and inhibits activities mediated by the IgG Fc domain, contributing to immune evasion by HSV. It has been reported that HSV type 1 gE (gE-1) is capable of binding IgG Fc as a monomer and in a heterodimeric complex with gI, with the heterodimer having 50- to100-fold greater affinity for Fc than gE alone. We report the production of both a soluble form of HSV type 2 gE (gE-2) and a soluble HSV-2 gE/gI heterodimer (gE-2/gI-2). Characterization of soluble gE-2 by surface plasmon resonance (SPR) demonstrates that it is incapable of binding human IgG or the IgG Fc domain. Co-expression with HSV-2 gI (gI-2) and purification of the gE-2/gI-2 heterodimer enable gE-2 to bind human IgG through its Fc domain. We hypothesize that functional epitopes of wildtype gE-2 may be masked by plasma IgG Fc and affect the immunogenicity of the gE-2/gI-2 heterodimer as a vaccine antigen. A series of gE-2 mutations within the surface-exposed Fc:gE-2 interface was designed, and gE-2 mutants were co-expressed with gI-2. Evaluation of twelve gE-2 mutant heterodimers by SPR assay identified nine gE-2 mutations which abrogated or reduced Fc binding while maintaining heterodimer formation with gI. Vaccinating rabbits with the four most Fc-binding deficient gE-2/gI-2 heterodimers elicited comparable anti-heterodimer binding antibody titers and statistically significantly higher serum neutralization antibody levels than wildtype heterodimers. Taken together, these data support the concept of rational antigen design for improved vaccine candidates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Vaccines (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Vaccines (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza