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.
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.
Authors: D Kumar; S Chernenko; G Moussa; I Cobos; O Manuel; J Preiksaitis; S Venkataraman; A Humar Journal: Am J Transplant Date: 2009-05 Impact factor: 8.086
Authors: Oksana A Shlobin; Erin E West; Noah Lechtzin; Susan M Miller; Marvin Borja; Jonathan B Orens; Lesia K Dropulic; John F McDyer Journal: J Immunol Date: 2006-02-15 Impact factor: 5.422
Authors: Martina Sester; Urban Sester; Barbara C Gärtner; Matthias Girndt; Andreas Meyerhans; Hans Köhler Journal: J Am Soc Nephrol Date: 2002-10 Impact factor: 10.121
Authors: Julie H Ishida; Tracy Burgess; Michael A Derby; Pearline A Brown; Mauricio Maia; Rong Deng; Brinda Emu; Becket Feierbach; Ashley E Fouts; X Charlene Liao; Jorge A Tavel Journal: Antimicrob Agents Chemother Date: 2015-06-08 Impact factor: 5.191
Authors: Michael A McVoy; Jian Ben Wang; Dirk P Dittmer; Craig J Bierle; Elizabeth C Swanson; Claudia Fernández-Alarcón; Nelmary Hernandez-Alvarado; Jason C Zabeli; Mark R Schleiss Journal: J Virol Date: 2016-08-12 Impact factor: 5.103
Authors: Meghan K Eberhardt; Ashlesha Deshpande; Joseph Fike; Rebecca Short; Kimberli A Schmidt; Shelley A Blozis; Mark R Walter; Peter A Barry Journal: J Virol Date: 2016-10-14 Impact factor: 5.103
Authors: Nicole Büscher; Christina Paulus; Michael Nevels; Stefan Tenzer; Bodo Plachter Journal: Med Microbiol Immunol Date: 2015-03-03 Impact factor: 3.402
Authors: Felix Wussow; Yujuan Yue; Joy Martinez; Jesse D Deere; Jeff Longmate; Andreas Herrmann; Peter A Barry; Don J Diamond Journal: J Virol Date: 2012-11-14 Impact factor: 5.103