Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model.
Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity confers partial protection. However, poorly un...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011378&type=printable |
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| author | Claire E Otero Richard Barfield Elizabeth Scheef Cody S Nelson Nicole Rodgers Hsuan-Yuan Wang Matilda J Moström Tabitha D Manuel Julian Sass Kimberli Schmidt Husam Taher Courtney Papen Lesli Sprehe Savannah Kendall Angel Davalos Peter A Barry Klaus Früh Justin Pollara Daniel Malouli Cliburn Chan Amitinder Kaur Sallie R Permar |
| author_facet | Claire E Otero Richard Barfield Elizabeth Scheef Cody S Nelson Nicole Rodgers Hsuan-Yuan Wang Matilda J Moström Tabitha D Manuel Julian Sass Kimberli Schmidt Husam Taher Courtney Papen Lesli Sprehe Savannah Kendall Angel Davalos Peter A Barry Klaus Früh Justin Pollara Daniel Malouli Cliburn Chan Amitinder Kaur Sallie R Permar |
| author_sort | Claire E Otero |
| collection | DOAJ |
| description | Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity confers partial protection. However, poorly understood immune correlates of protection against placental transmission contributes to the current lack of an approved vaccine to prevent cCMV. In this study, we characterized the kinetics of maternal plasma rhesus CMV (RhCMV) viral load (VL) and RhCMV-specific antibody binding and functional responses in a group of 12 immunocompetent dams with acute, primary RhCMV infection. We defined cCMV transmission as RhCMV detection in amniotic fluid (AF) by qPCR. We then leveraged a large group of past and current primary RhCMV infection studies in late-first/early-second trimester RhCMV-seronegative rhesus macaque dams, including immunocompetent (n = 15), CD4+ T cell-depleted with (n = 6) and without (n = 6) RhCMV-specific polyclonal IgG infusion before infection to evaluate differences between RhCMV AF-positive and AF-negative dams. During the first 3 weeks after infection, the magnitude of RhCMV VL in maternal plasma was higher in AF-positive dams in the combined cohort, while RhCMV glycoprotein B (gB)- and pentamer-specific binding IgG responses were lower magnitude compared to AF-negative dams. However, these observed differences were driven by the CD4+ T cell-depleted dams, as there were no differences in plasma VL or antibody responses between immunocompetent AF-positive vs AF-negative dams. Overall, these results suggest that levels of neither maternal plasma viremia nor humoral responses are associated with cCMV following primary maternal infection in healthy individuals. We speculate that other factors related to innate immunity are more important in this context as antibody responses to acute infection likely develop too late to influence vertical transmission. Yet, pre-existing CMV glycoprotein-specific and neutralizing IgG may provide protection against cCMV following primary maternal CMV infection even in high-risk, immunocompromised settings. |
| first_indexed | 2024-03-08T03:11:09Z |
| format | Article |
| id | doaj.art-c5d4db2c414e4452a4d70b4bd935fc85 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-08T03:11:09Z |
| publishDate | 2023-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-c5d4db2c414e4452a4d70b4bd935fc852024-02-13T05:32:29ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-10-011910e101137810.1371/journal.ppat.1011378Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model.Claire E OteroRichard BarfieldElizabeth ScheefCody S NelsonNicole RodgersHsuan-Yuan WangMatilda J MoströmTabitha D ManuelJulian SassKimberli SchmidtHusam TaherCourtney PapenLesli SpreheSavannah KendallAngel DavalosPeter A BarryKlaus FrühJustin PollaraDaniel MalouliCliburn ChanAmitinder KaurSallie R PermarCytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity confers partial protection. However, poorly understood immune correlates of protection against placental transmission contributes to the current lack of an approved vaccine to prevent cCMV. In this study, we characterized the kinetics of maternal plasma rhesus CMV (RhCMV) viral load (VL) and RhCMV-specific antibody binding and functional responses in a group of 12 immunocompetent dams with acute, primary RhCMV infection. We defined cCMV transmission as RhCMV detection in amniotic fluid (AF) by qPCR. We then leveraged a large group of past and current primary RhCMV infection studies in late-first/early-second trimester RhCMV-seronegative rhesus macaque dams, including immunocompetent (n = 15), CD4+ T cell-depleted with (n = 6) and without (n = 6) RhCMV-specific polyclonal IgG infusion before infection to evaluate differences between RhCMV AF-positive and AF-negative dams. During the first 3 weeks after infection, the magnitude of RhCMV VL in maternal plasma was higher in AF-positive dams in the combined cohort, while RhCMV glycoprotein B (gB)- and pentamer-specific binding IgG responses were lower magnitude compared to AF-negative dams. However, these observed differences were driven by the CD4+ T cell-depleted dams, as there were no differences in plasma VL or antibody responses between immunocompetent AF-positive vs AF-negative dams. Overall, these results suggest that levels of neither maternal plasma viremia nor humoral responses are associated with cCMV following primary maternal infection in healthy individuals. We speculate that other factors related to innate immunity are more important in this context as antibody responses to acute infection likely develop too late to influence vertical transmission. Yet, pre-existing CMV glycoprotein-specific and neutralizing IgG may provide protection against cCMV following primary maternal CMV infection even in high-risk, immunocompromised settings.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011378&type=printable |
| spellingShingle | Claire E Otero Richard Barfield Elizabeth Scheef Cody S Nelson Nicole Rodgers Hsuan-Yuan Wang Matilda J Moström Tabitha D Manuel Julian Sass Kimberli Schmidt Husam Taher Courtney Papen Lesli Sprehe Savannah Kendall Angel Davalos Peter A Barry Klaus Früh Justin Pollara Daniel Malouli Cliburn Chan Amitinder Kaur Sallie R Permar Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. PLoS Pathogens |
| title | Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. |
| title_full | Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. |
| title_fullStr | Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. |
| title_full_unstemmed | Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. |
| title_short | Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model. |
| title_sort | relationship of maternal cytomegalovirus specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011378&type=printable |
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