Journal of Clinical Immunology

, Volume 32, Issue 6, pp 1324–1331 | Cite as

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

  • Daniele Lilleri
  • Anna Kabanova
  • Antonio Lanzavecchia
  • Giuseppe Gerna
Article

Abstract

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.

Keywords

Human cytomegalovirus neutralizing antibodies virus dissemination protection pentamer complex epitopes 

Notes

Acknowledgments

The authors thank the technical staffs of the two collaborating laboratories. In addition, they like to thank Daniela Sartori for careful manuscript editing and Laurene Kelly for revision of the English. This work was partially supported by grants from Fondazione CARIPLO, Milan, Italy (grant 93043/A), and by Fondazione Carlo Denegri, Turin, Italy.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Daniele Lilleri
    • 1
  • Anna Kabanova
    • 2
  • Antonio Lanzavecchia
    • 2
  • Giuseppe Gerna
    • 1
  1. 1.Laboratori Sperimentali di Ricerca, Area TrapiantologicaFondazione IRCCS Policlinico San MatteoPaviaItaly
  2. 2.Institute for Research in BiomedicineBellinzonaSwitzerland

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