Antibodies Against Neutralization Epitopes of Human Cytomegalovirus gH/gL/pUL128-130-131 Complex and Virus Spreading May Correlate with Virus Control In Vivo

• Published in: Journal of clinical immunology Vol. 32; no. 6; pp. 1324 - 1331
• Main Authors: Lilleri, Daniele, Kabanova, Anna, Lanzavecchia, Antonio, Gerna, Giuseppe
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2012; Springer Nature B.V
• Subjects: Antibodies; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibodies, Viral - immunology; Binding, Competitive; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Cell migration; Cell spreading; Coculture Techniques; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - transmission; Cytomegalovirus Infections - virology; Endothelial cells; Endothelial Cells - immunology; Endothelial Cells - virology; Enzyme-Linked Immunosorbent Assay; Epitopes; Epitopes - genetics; Epitopes - immunology; Female; Fetuses; Glycoprotein H; Glycoproteins; Human cytomegalovirus; Humans; Immunology; Infectious Disease Transmission, Vertical; Infectious Diseases; Internal Medicine; Leukocytes; Leukocytes - immunology; Leukocytes - virology; Medical Microbiology; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Monoclonal antibodies; Neutralization Tests; Pregnancy; Protein Multimerization; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Plaque Assay; Viral Proteins - genetics; Viral Proteins - immunology; epitopes; neutralizing antibodies; pentamer complex; protection; virus dissemination; Human cytomegalovirus
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-012-9739-3

Purpose Recently, human cytomegalovirus (HCMV) UL128-131 locus gene products have been found to be associated with glycoprotein H (gH) and glycoprotein L (gL) to form a pentameric glycoprotein complex gH/gL/pUL128-130-131, which is present in the virus envelope and elicits production of neutralizing antibodies. Purpose of this study was to verify whether in vitro activities of these antibodies may correlate with protection in vivo . Methods By using potently neutralizing human monoclonal antibodies (mAbs) targeting 10 different epitopes of the pentameric complex, a competitive ELISA assay was developed, in which the pentamer bound to the solid-phase was reacted competitively with human sera and murinized human mAbs. In addition, inhibition of virus spreading (plaque formation and leukocyte transfer) by neutralizing human mAbs and sera was investigated. Results In the absence of any reactivity of sera from HCMV-seronegative subjects, antibodies to all 10 epitopes were detected in HCMV-seropositive individuals. During primary HCMV infection in pregnancy antibodies to some epitopes showed a trend towards an earlier appearance in mothers not transmitting the virus to the fetus as compared to transmitting mothers. In addition, the activity of neutralizing human mAbs and sera in blocking virus cell-to-cell spreading and virus transfer to leukocytes from infected endothelial cells was shown to develop during the convalescent phase of primary infection. Conclusions Dissection of the neutralizing/inhibiting activities of human sera may be helpful in the study of their protective role in vivo . In particular, neutralizing antibodies to the pentamer may be a surrogate marker of protection in vivo .