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116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition

BACKGROUND: Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. Development of an effective CMV vaccine is a public health priority. However, CMV vaccine development is limited by a poor understanding of the immune correlates of protection, includi...

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Autores principales: Saccoccio, Frances, Itell, Hannah, Li, Skukhang, Jenks, Jennifer, Xie, Guan, Pollara, Justin, Gantt, Soren, Permar, Sallie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252909/
http://dx.doi.org/10.1093/ofid/ofy209.007
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author Saccoccio, Frances
Itell, Hannah
Li, Skukhang
Jenks, Jennifer
Xie, Guan
Pollara, Justin
Gantt, Soren
Permar, Sallie
author_facet Saccoccio, Frances
Itell, Hannah
Li, Skukhang
Jenks, Jennifer
Xie, Guan
Pollara, Justin
Gantt, Soren
Permar, Sallie
author_sort Saccoccio, Frances
collection PubMed
description BACKGROUND: Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. Development of an effective CMV vaccine is a public health priority. However, CMV vaccine development is limited by a poor understanding of the immune correlates of protection, including the role of CMV-specific IgG. Defining the role of passively acquired maternal IgG in the protection of half of the CMV-exposed, breastfeeding infants against postnatal CMV acquisition may inform CMV vaccine design METHODS: We analyzed CMV-specific humoral responses in 29 CMV-seropositive Ugandan mother–infant pairs. Seventeen mothers were HIV co-infected. Infants were followed weekly for postnatal CMV acquisition using saliva PCR. Twelve infants acquired CMV and 17 infants did not acquire CMV in the first 6 months of life. We compared CMV-specific IgG responses at delivery of mothers whose infants acquired CMV to mothers whose infants did not acquire CMV by 6 months of life and in the infants at 6 weeks of life. We also compared CMV-specific responses in mothers at delivery and infants at 6 weeks of life based on maternal HIV status. RESULTS: We found similar CMV-specific total IgG and IgG3 binding, avidity index, neutralization, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity responses in mothers whose infants did or did not acquire CMV by 6 months of life. Moreover, similar CMV-specific IgG binding and neutralization responses were also found between infants who did or did not acquire CMV by 6 months of life. Finally, CMV-specific IgG responses were similar in HIV-infected and uninfected mothers at delivery and in infants at 6 weeks of life regardless of perinatal HIV exposure. CONCLUSION: CMV-binding and functional IgG responses do not appear to impact infant susceptibility to postnatal CMV acquisition in the first 6 months of life, and therefore other viral or immunologic factors contribute to the inefficiency of this mode of CMV transmission. Thus, to provide sterilizing protection against mucosal CMV acquisition, an antibody-based CMV vaccine would likely have to induce higher magnitude or qualitatively different responses than that of natural infection. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-62529092018-11-28 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition Saccoccio, Frances Itell, Hannah Li, Skukhang Jenks, Jennifer Xie, Guan Pollara, Justin Gantt, Soren Permar, Sallie Open Forum Infect Dis Abstracts BACKGROUND: Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. Development of an effective CMV vaccine is a public health priority. However, CMV vaccine development is limited by a poor understanding of the immune correlates of protection, including the role of CMV-specific IgG. Defining the role of passively acquired maternal IgG in the protection of half of the CMV-exposed, breastfeeding infants against postnatal CMV acquisition may inform CMV vaccine design METHODS: We analyzed CMV-specific humoral responses in 29 CMV-seropositive Ugandan mother–infant pairs. Seventeen mothers were HIV co-infected. Infants were followed weekly for postnatal CMV acquisition using saliva PCR. Twelve infants acquired CMV and 17 infants did not acquire CMV in the first 6 months of life. We compared CMV-specific IgG responses at delivery of mothers whose infants acquired CMV to mothers whose infants did not acquire CMV by 6 months of life and in the infants at 6 weeks of life. We also compared CMV-specific responses in mothers at delivery and infants at 6 weeks of life based on maternal HIV status. RESULTS: We found similar CMV-specific total IgG and IgG3 binding, avidity index, neutralization, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity responses in mothers whose infants did or did not acquire CMV by 6 months of life. Moreover, similar CMV-specific IgG binding and neutralization responses were also found between infants who did or did not acquire CMV by 6 months of life. Finally, CMV-specific IgG responses were similar in HIV-infected and uninfected mothers at delivery and in infants at 6 weeks of life regardless of perinatal HIV exposure. CONCLUSION: CMV-binding and functional IgG responses do not appear to impact infant susceptibility to postnatal CMV acquisition in the first 6 months of life, and therefore other viral or immunologic factors contribute to the inefficiency of this mode of CMV transmission. Thus, to provide sterilizing protection against mucosal CMV acquisition, an antibody-based CMV vaccine would likely have to induce higher magnitude or qualitatively different responses than that of natural infection. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2018-11-26 /pmc/articles/PMC6252909/ http://dx.doi.org/10.1093/ofid/ofy209.007 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Saccoccio, Frances
Itell, Hannah
Li, Skukhang
Jenks, Jennifer
Xie, Guan
Pollara, Justin
Gantt, Soren
Permar, Sallie
116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
title 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
title_full 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
title_fullStr 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
title_full_unstemmed 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
title_short 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition
title_sort 116. role of maternal antibodies in protection against postnatal cytomegalovirus acquisition
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252909/
http://dx.doi.org/10.1093/ofid/ofy209.007
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