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.
Division of Virology, Department of Pathology, University of Cambridge, UK.
Janet S
JS
May
Philip G
PG
Stevenson
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