BACKGROUND: Recently, a new human cytomegalovirus (HCMV) glycoprotein complex has been identified and potentially proposed as a vaccine. OBJECTIVE: The aim of this study was to determine whether the HCMV gH/gL/pUL128-pUL130-pUL131 (gH/gL/pUL128-131) 5-protein (pentameric) complex (which has been recently found to be indispensable for the infection of endothelial and epithelial cells) is able to elicit a consistent antibody response in both primary and reactivated HCMV infections. STUDY DESIGN: The antibody response was determined by both indirect immunofluorescence (IFA) and ELISA, using fixed (IFA) or lysed (ELISA) epithelial (ARPE-19) cells infected with one or more adenoviral vectors, each carrying one HCMV gene and, in parallel, with a control adenovirus vector. RESULTS: The specificity of results was determined by the reactivity of human neutralizing mAbs recognizing two, three, or four proteins of the complex. In 14 cases of primary infection, an IgG antibody seroconversion to the UL128-131 gene products was consistently detected within 2-4 weeks after onset of infection, while antibodies persisted for at least 12 months. The IgG antibody response to UL128-131 gene products was generally superior to the response to gH and appeared to follow the neutralizing antibody response (as determined in epithelial cells). In reactivated infections, the antibody response showed a trend reminiscent of a booster response. IgG antibodies were detected in HCMV-seropositive healthy adult controls, but not in HCMV-seronegative individuals. CONCLUSIONS: The IgG antibody response to the pentameric complex could be a major target for the evaluation of the antibody response to a pentamer-based vaccine.
BACKGROUND: Recently, a new human cytomegalovirus (HCMV) glycoprotein complex has been identified and potentially proposed as a vaccine. OBJECTIVE: The aim of this study was to determine whether the HCMV gH/gL/pUL128-pUL130-pUL131 (gH/gL/pUL128-131) 5-protein (pentameric) complex (which has been recently found to be indispensable for the infection of endothelial and epithelial cells) is able to elicit a consistent antibody response in both primary and reactivated HCMV infections. STUDY DESIGN: The antibody response was determined by both indirect immunofluorescence (IFA) and ELISA, using fixed (IFA) or lysed (ELISA) epithelial (ARPE-19) cells infected with one or more adenoviral vectors, each carrying one HCMV gene and, in parallel, with a control adenovirus vector. RESULTS: The specificity of results was determined by the reactivity of human neutralizing mAbs recognizing two, three, or four proteins of the complex. In 14 cases of primary infection, an IgG antibody seroconversion to the UL128-131 gene products was consistently detected within 2-4 weeks after onset of infection, while antibodies persisted for at least 12 months. The IgG antibody response to UL128-131 gene products was generally superior to the response to gH and appeared to follow the neutralizing antibody response (as determined in epithelial cells). In reactivated infections, the antibody response showed a trend reminiscent of a booster response. IgG antibodies were detected in HCMV-seropositive healthy adult controls, but not in HCMV-seronegative individuals. CONCLUSIONS: The IgG antibody response to the pentameric complex could be a major target for the evaluation of the antibody response to a pentamer-based vaccine.
Authors: Claudio Ciferri; Sumana Chandramouli; Danilo Donnarumma; Pavel A Nikitin; Michael A Cianfrocco; Rachel Gerrein; Adam L Feire; Susan W Barnett; Anders E Lilja; Rino Rappuoli; Nathalie Norais; Ethan C Settembre; Andrea Carfi Journal: Proc Natl Acad Sci U S A Date: 2015-01-26 Impact factor: 11.205
Authors: Rachel B Gill; J Jason Bowman; Tammy Krogmann; Kurt Wollenberg; David M Asher; Jeffrey I Cohen Journal: Virology Date: 2013-10-02 Impact factor: 3.616
Authors: Devon J Shedlock; Kendra T Talbott; Stephan J Wu; Christine M Wilson; Karuppiah Muthumani; Jean D Boyer; Niranjan Y Sardesai; Sita Awasthi; David B Weiner Journal: Hum Vaccin Immunother Date: 2012-11-01 Impact factor: 3.452
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