Neutralizing and ELISA IgG antibodies to human cytomegalovirus glycoprotein complexes may help date the onset of primary infection in pregnancy

Background: Definition of onset for primary human cytomegalovirus (HCMV) infection during pregnancy is critical for several reasons, including diagnosis of pre-conceptional infections and definition of gestational age at the time of infection. Objective: To determine the onset of primary HCMV infection, differential kinetics of antibodies neutralizing infection of epithelial and fibroblast cells, as well as ELISA IgG antibodies to HCMV glycoprotein complexes (gC) gH/gL/pUL128L, gH/gL/gO, and gB were exploited and compared with conventional assays. Study design: In a series of 40 pregnant women with primary HCMV infection and ascertained HCMV-related mild clinical symptoms, the kinetics of different types of neutralizing and ELISA IgG antibodies were investigated with the aim of establishing criteria for dating the onset of primary infection in pregnant women without clinical symptoms. Results: IgG antibodies to gB and gH/gL/pUL128L, as well as antibodies neutralizing infection of epithelial cells appeared early after infection onset (within 2-3 weeks) and increased rapidly, whereas antibodies to gH/gL/gO and antibodies neutralizing infection of fibroblasts appeared later (>30 days) and increased slowly. Both the conventional diagnostic assays (IgG, and IgM antibody, and IgG avidity index) and the novel assays for determination of antibody responses directed against HCMV gC allowed the definition of an algorithm indicating the onset of primary HCMV infection in asymptomatic women within a period of 1-2 months. Conclusion: New neutralization and ELISA IgG assays to HCMV gC provide additional tools for dating the onset of primary infection in pregnancy.