Complement enhances in vitro neutralizing potency of antibodies to human cytomegalovirus glycoprotein B (Gb) and immune sera induced by Gb/MF59 vaccination /631/250/590/2294 /692/53/2423 article

Fengsheng Li, Daniel C. Freed, Aimin Tang, Richard R. Rustandi, Matthew C. Troutman, Amy S. Espeseth, Ningyan Zhang, Zhiqiang An, Michael McVoy, Hua Zhu, Sha Ha, Dai Wang, Stuart P. Adler, Tong Ming Fu

Research output: Contribution to journalArticle

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Abstract

Human cytomegalovirus (HCMV) is the leading cause of in utero viral infection in the United States. Since congenital HCMV infection can lead to birth defects in newborns, developing a prophylactic vaccine is a high priority. One of the early experimental vaccines, composed of a recombinant glycoprotein B (gB) formulated with MF59 adjuvant, has demonstrated approximately 50% efficacy against HCMV infection in seronegative women. Using immune sera from two gB/MF59 Phase 1 studies in humans we showed that complement can enhance the in vitro HCMV neutralizing potency of antibodies induced by the gB/MF59 vaccination. To characterize this complement-dependent antiviral activity, we analyzed three rabbit non-neutralizing gB monoclonal antibodies (mAbs) with different biochemical profiles including epitope specificity. Two of the three mAbs, r272.7 and r210.4, exhibited neutralizing activity when complement was added to the assays, and this complement-dependent antiviral activity was not related to the antibody's affinity to gB but appeared to be associated with their epitope specificities. Moreover, neutralization could only be demonstrated when complement was present at or before viral entry, suggesting that IgG Fc-mediated function was not the basis for this antiviral activity. Lastly, we demonstrated that gB/MF59 immune sera contained antibodies that can cross-compete with r272.7 for gB binding and that the titers of these antibodies correlated with complement-dependent neutralization titers. These results suggested that gB antibodies with certain biochemical properties have neutralizing potency when complement is present and that this complement-dependent antiviral activity may be a part of immune components which conferred protection against HCMV infection by gB/MF59 vaccination.

Original languageEnglish (US)
Article number38
Journalnpj Vaccines
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2017

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Neutralizing Antibodies
Immune Sera
Glycoproteins
Vaccination
Antiviral Agents
Cytomegalovirus Infections
Cytomegalovirus
Antibodies
Epitopes
Vaccines
Monoclonal Antibodies
Antibody Affinity
In Vitro Techniques
Simplexvirus glycoprotein B
MF59 oil emulsion
Virus Diseases
Immunoglobulin G
Newborn Infant
Rabbits

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Li, Fengsheng ; Freed, Daniel C. ; Tang, Aimin ; Rustandi, Richard R. ; Troutman, Matthew C. ; Espeseth, Amy S. ; Zhang, Ningyan ; An, Zhiqiang ; McVoy, Michael ; Zhu, Hua ; Ha, Sha ; Wang, Dai ; Adler, Stuart P. ; Fu, Tong Ming. / Complement enhances in vitro neutralizing potency of antibodies to human cytomegalovirus glycoprotein B (Gb) and immune sera induced by Gb/MF59 vaccination /631/250/590/2294 /692/53/2423 article. In: npj Vaccines. 2017 ; Vol. 2, No. 1.
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abstract = "Human cytomegalovirus (HCMV) is the leading cause of in utero viral infection in the United States. Since congenital HCMV infection can lead to birth defects in newborns, developing a prophylactic vaccine is a high priority. One of the early experimental vaccines, composed of a recombinant glycoprotein B (gB) formulated with MF59 adjuvant, has demonstrated approximately 50{\%} efficacy against HCMV infection in seronegative women. Using immune sera from two gB/MF59 Phase 1 studies in humans we showed that complement can enhance the in vitro HCMV neutralizing potency of antibodies induced by the gB/MF59 vaccination. To characterize this complement-dependent antiviral activity, we analyzed three rabbit non-neutralizing gB monoclonal antibodies (mAbs) with different biochemical profiles including epitope specificity. Two of the three mAbs, r272.7 and r210.4, exhibited neutralizing activity when complement was added to the assays, and this complement-dependent antiviral activity was not related to the antibody's affinity to gB but appeared to be associated with their epitope specificities. Moreover, neutralization could only be demonstrated when complement was present at or before viral entry, suggesting that IgG Fc-mediated function was not the basis for this antiviral activity. Lastly, we demonstrated that gB/MF59 immune sera contained antibodies that can cross-compete with r272.7 for gB binding and that the titers of these antibodies correlated with complement-dependent neutralization titers. These results suggested that gB antibodies with certain biochemical properties have neutralizing potency when complement is present and that this complement-dependent antiviral activity may be a part of immune components which conferred protection against HCMV infection by gB/MF59 vaccination.",
author = "Fengsheng Li and Freed, {Daniel C.} and Aimin Tang and Rustandi, {Richard R.} and Troutman, {Matthew C.} and Espeseth, {Amy S.} and Ningyan Zhang and Zhiqiang An and Michael McVoy and Hua Zhu and Sha Ha and Dai Wang and Adler, {Stuart P.} and Fu, {Tong Ming}",
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Complement enhances in vitro neutralizing potency of antibodies to human cytomegalovirus glycoprotein B (Gb) and immune sera induced by Gb/MF59 vaccination /631/250/590/2294 /692/53/2423 article. / Li, Fengsheng; Freed, Daniel C.; Tang, Aimin; Rustandi, Richard R.; Troutman, Matthew C.; Espeseth, Amy S.; Zhang, Ningyan; An, Zhiqiang; McVoy, Michael; Zhu, Hua; Ha, Sha; Wang, Dai; Adler, Stuart P.; Fu, Tong Ming.

In: npj Vaccines, Vol. 2, No. 1, 38, 01.12.2017.

Research output: Contribution to journalArticle

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T1 - Complement enhances in vitro neutralizing potency of antibodies to human cytomegalovirus glycoprotein B (Gb) and immune sera induced by Gb/MF59 vaccination /631/250/590/2294 /692/53/2423 article

AU - Li, Fengsheng

AU - Freed, Daniel C.

AU - Tang, Aimin

AU - Rustandi, Richard R.

AU - Troutman, Matthew C.

AU - Espeseth, Amy S.

AU - Zhang, Ningyan

AU - An, Zhiqiang

AU - McVoy, Michael

AU - Zhu, Hua

AU - Ha, Sha

AU - Wang, Dai

AU - Adler, Stuart P.

AU - Fu, Tong Ming

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Human cytomegalovirus (HCMV) is the leading cause of in utero viral infection in the United States. Since congenital HCMV infection can lead to birth defects in newborns, developing a prophylactic vaccine is a high priority. One of the early experimental vaccines, composed of a recombinant glycoprotein B (gB) formulated with MF59 adjuvant, has demonstrated approximately 50% efficacy against HCMV infection in seronegative women. Using immune sera from two gB/MF59 Phase 1 studies in humans we showed that complement can enhance the in vitro HCMV neutralizing potency of antibodies induced by the gB/MF59 vaccination. To characterize this complement-dependent antiviral activity, we analyzed three rabbit non-neutralizing gB monoclonal antibodies (mAbs) with different biochemical profiles including epitope specificity. Two of the three mAbs, r272.7 and r210.4, exhibited neutralizing activity when complement was added to the assays, and this complement-dependent antiviral activity was not related to the antibody's affinity to gB but appeared to be associated with their epitope specificities. Moreover, neutralization could only be demonstrated when complement was present at or before viral entry, suggesting that IgG Fc-mediated function was not the basis for this antiviral activity. Lastly, we demonstrated that gB/MF59 immune sera contained antibodies that can cross-compete with r272.7 for gB binding and that the titers of these antibodies correlated with complement-dependent neutralization titers. These results suggested that gB antibodies with certain biochemical properties have neutralizing potency when complement is present and that this complement-dependent antiviral activity may be a part of immune components which conferred protection against HCMV infection by gB/MF59 vaccination.

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