Vaccination with murid herpesvirus-4 glycoprotein B reduces viral lytic replication but does not induce detectable virion neutralization.
Herpesviruses characteristically disseminate from immune hosts. Therefore in the context of natural infection, antibody neutralizes them poorly. Murid herpesvirus-4 (MuHV-4) provides a tractable model with which to understand gammaherpesvirus neutralization. MuHV-4 virions blocked for cell binding by immune sera remain infectious for IgG-Fc receptor(+) myeloid cells, so broadly neutralizing antibodies must target the virion fusion complex - glycoprotein B (gB) or gH/gL. While gB-specific neutralizing antibodies are rare, its domains I+II (gB-N) contain at least one potent neutralization epitope. Here, we tested whether immunization with recombinant gB presenting this epitope could induce neutralizing antibodies in naive mice and protect them against MuHV-4 challenge. Immunizing with the full-length gB extracellular domain induced a strong gB-specific antibody response and reduced MuHV-4 lytic replication but did not induce detectable neutralization. gB-N alone, which more selectively displayed pre-fusion epitopes including neutralization epitopes, also failed to induce neutralizing responses, and while viral lytic replication was again reduced this depended completely on IgG Fc receptors. gB and gB-N also boosted neutralizing responses in only a minority of carrier mice. Therefore, it appears that neutralizing epitopes on gB are intrinsically difficult for the immune response to target.
May
Janet S
JS
Division of Virology, Department of Pathology, University of Cambridge, UK.
Stevenson
Philip G
PG
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood; D006023:Glycoproteins / Q000276:immunology*; D006566:Herpesviridae Infections / Q000517:prevention & control*; D022283:Herpesvirus Vaccines / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000276:immunology; D018144:Rhadinovirus / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D022283:Herpesvirus Vaccines; D007074:Immunoglobulin G; D017452:Receptors, IgG; D014614:Vaccines, Synthetic; D014764:Viral Proteins