Antibodies to the major linear neutralizing domains of cytomegalovirus glycoprotein B among natural seropositives and CMV subunit vaccine recipients

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) lackin g heavily glycosylated intervening regions, the transmembrane domain, and t he cytoplasmic domain, was expressed in recombinant baculovirus-infected ce lls. Eighty-six percent of 600 naturally CMV-seropositive individuals and 9 3% of 121 gB vaccine recipients had antibodies to Delta-gB as detected by e nzyme-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 a nd 7% of 120 gB vaccinees lacked Delta-gB antibodies but had neutralizing a ctivity. Among subjects with Delta-gB antibody, there were weak correlation s between antibody level and neutralizing titer, These data suggest that an tibodies to linear neutralizing gB domains are highly prevalent in naturall y-infected individuals and regularly develop in gB vaccinees, However, for some individuals, discontinuous and/or linear epitopes not represented on D elta-gB may be more important in the generation of neutralizing responses.