title: Antibodies to the major linear neutralizing domains of cytomegalovirus glycoprotein B among natural seropositives and CMV subunit vaccine recipients.
abstract: The gB protein (gpUL55) of human cytomegalovirus (CMV) contains C-terminal (AD-1) and N-terminal (AD-2) linear immunodominant neutralizing domains. To measure antibodies to these epitopes, a modified protein (delta-gB) lacking heavily glycosylated intervening regions, the transmembrane domain, and the cytoplasmic domain, was expressed in recombinant baculovirus-infected cells. Eighty-six percent of 600 naturally CMV-seropositive individuals and 93% of 121 gB vaccine recipients had antibodies to delta-gB as detected by enzyme-linked immunosorbent assay (ELISA). The antibody level in vaccinees (median optical density [OD] = 1.73) exceeded that in natural seropositives (median OD = 0.94; p < .0001). Eleven percent of 95 natural seropositives and 7% of 120 gB vaccinees lacked A-gB antibodies but had neutralizing activity. Among subjects with delta-gB antibody, there were weak correlations between antibody level and neutralizing titer. These data suggest that antibodies to linear neutralizing gB domains are highly prevalent in naturally-infected individuals and regularly develop in gB vaccinees. However, for some individuals, discontinuous and/or linear epitopes not represented on delta-gB may be more important in the generation of neutralizing responses.
authors.affiliation: Department of Pediatrics, University of Louisville School of Medicine, Kentucky 40202, USA. gsmars01@athena.louisville.edu
authors.forename: G S
authors.initials: GS
authors.lastname: Marshall
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: G G
authors.initials: GG
authors.lastname: Stout
authors.forename: M V
authors.initials: MV
authors.lastname: Louthan
authors.forename: A M
authors.initials: AM
authors.lastname: Duliège
authors.forename: R L
authors.initials: RL
authors.lastname: Burke
authors.forename: L A
authors.initials: LA
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus