Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model
IntroductionZika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267638/full |
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| author | Nicholas P. Krabbe Elaina Razo Hunter J. Abraham Rachel V. Spanton Yujia Shi Saswati Bhattacharya Ellie K. Bohm Julia C. Pritchard Andrea M. Weiler Ann M. Mitzey Jens C. Eickhoff Eric Sullivan John C. Tan Matthew T. Aliota Thomas C. Friedrich Thomas C. Friedrich David H. O’Connor David H. O’Connor Thaddeus G. Golos Thaddeus G. Golos Thaddeus G. Golos Emma L. Mohr |
| author_facet | Nicholas P. Krabbe Elaina Razo Hunter J. Abraham Rachel V. Spanton Yujia Shi Saswati Bhattacharya Ellie K. Bohm Julia C. Pritchard Andrea M. Weiler Ann M. Mitzey Jens C. Eickhoff Eric Sullivan John C. Tan Matthew T. Aliota Thomas C. Friedrich Thomas C. Friedrich David H. O’Connor David H. O’Connor Thaddeus G. Golos Thaddeus G. Golos Thaddeus G. Golos Emma L. Mohr |
| author_sort | Nicholas P. Krabbe |
| collection | DOAJ |
| description | IntroductionZika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes.MethodsHere, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized.ResultsDams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection.DiscussionThus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further. |
| first_indexed | 2024-03-11T22:39:24Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T22:39:24Z |
| publishDate | 2023-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-fc3e7c5657814d8791677bf87f7d17872023-09-22T09:24:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12676381267638Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque modelNicholas P. Krabbe0Elaina Razo1Hunter J. Abraham2Rachel V. Spanton3Yujia Shi4Saswati Bhattacharya5Ellie K. Bohm6Julia C. Pritchard7Andrea M. Weiler8Ann M. Mitzey9Jens C. Eickhoff10Eric Sullivan11John C. Tan12Matthew T. Aliota13Thomas C. Friedrich14Thomas C. Friedrich15David H. O’Connor16David H. O’Connor17Thaddeus G. Golos18Thaddeus G. Golos19Thaddeus G. Golos20Emma L. Mohr21Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota-Twin Cities, St. Paul, MN, United StatesDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota-Twin Cities, St. Paul, MN, United StatesWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Biostatistics and Medical Informatics, School of Medicine and Public Healthy, University of Wisconsin-Madison, Madison, WI, United StatesNimble Therapeutics, Inc, Madison, WI, United StatesNimble Therapeutics, Inc, Madison, WI, United StatesDepartment of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota-Twin Cities, St. Paul, MN, United StatesWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United StatesWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United StatesIntroductionZika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes.MethodsHere, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized.ResultsDams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection.DiscussionThus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267638/fullZika virusZIKVmacaque modelpregnancymaternal ZIKV infectioncongenital Zika syndrome (CZS) |
| spellingShingle | Nicholas P. Krabbe Elaina Razo Hunter J. Abraham Rachel V. Spanton Yujia Shi Saswati Bhattacharya Ellie K. Bohm Julia C. Pritchard Andrea M. Weiler Ann M. Mitzey Jens C. Eickhoff Eric Sullivan John C. Tan Matthew T. Aliota Thomas C. Friedrich Thomas C. Friedrich David H. O’Connor David H. O’Connor Thaddeus G. Golos Thaddeus G. Golos Thaddeus G. Golos Emma L. Mohr Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model Frontiers in Immunology Zika virus ZIKV macaque model pregnancy maternal ZIKV infection congenital Zika syndrome (CZS) |
| title | Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model |
| title_full | Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model |
| title_fullStr | Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model |
| title_full_unstemmed | Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model |
| title_short | Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model |
| title_sort | control of maternal zika virus infection during pregnancy is associated with lower antibody titers in a macaque model |
| topic | Zika virus ZIKV macaque model pregnancy maternal ZIKV infection congenital Zika syndrome (CZS) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267638/full |
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