Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection
Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immun...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical Investigation
2022-08-01
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| Series: | The Journal of Clinical Investigation |
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| Online Access: | https://doi.org/10.1172/JCI156827 |
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| author | Eleanor C. Semmes Itzayana G. Miller Courtney E. Wimberly Caroline T. Phan Jennifer A. Jenks Melissa J. Harnois Stella J. Berendam Helen Webster Jillian H. Hurst Joanne Kurtzberg Genevieve G. Fouda Kyle M. Walsh Sallie R. Permar |
| author_facet | Eleanor C. Semmes Itzayana G. Miller Courtney E. Wimberly Caroline T. Phan Jennifer A. Jenks Melissa J. Harnois Stella J. Berendam Helen Webster Jillian H. Hurst Joanne Kurtzberg Genevieve G. Fouda Kyle M. Walsh Sallie R. Permar |
| author_sort | Eleanor C. Semmes |
| collection | DOAJ |
| description | Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development. |
| first_indexed | 2024-03-11T12:09:22Z |
| format | Article |
| id | doaj.art-01cf6c8bdde642388fe306afd43ea024 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:09:22Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-01cf6c8bdde642388fe306afd43ea0242023-11-07T16:19:14ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-08-0113216Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infectionEleanor C. SemmesItzayana G. MillerCourtney E. WimberlyCaroline T. PhanJennifer A. JenksMelissa J. HarnoisStella J. BerendamHelen WebsterJillian H. HurstJoanne KurtzbergGenevieve G. FoudaKyle M. WalshSallie R. PermarHuman cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.https://doi.org/10.1172/JCI156827ImmunologyInfectious disease |
| spellingShingle | Eleanor C. Semmes Itzayana G. Miller Courtney E. Wimberly Caroline T. Phan Jennifer A. Jenks Melissa J. Harnois Stella J. Berendam Helen Webster Jillian H. Hurst Joanne Kurtzberg Genevieve G. Fouda Kyle M. Walsh Sallie R. Permar Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection The Journal of Clinical Investigation Immunology Infectious disease |
| title | Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection |
| title_full | Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection |
| title_fullStr | Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection |
| title_full_unstemmed | Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection |
| title_short | Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection |
| title_sort | maternal fc mediated non neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection |
| topic | Immunology Infectious disease |
| url | https://doi.org/10.1172/JCI156827 |
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