Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model

Frontiers in Immunology

Immunology

Jens C. Eickhoff¹  Ann M. Mitzey²  Nicholas P. Krabbe³  Rachel V. Spanton³  Yujia Shi³  Emma L. Mohr³  Elaina Razo³  Hunter J. Abraham³  Saswati Bhattacharya³  Julia C. Pritchard⁴  Ellie K. Bohm⁴  Matthew T. Aliota⁴  Eric Sullivan⁵  John C. Tan⁵  Andrea M. Weiler⁶  Thaddeus G. Golos⁷  Thomas C. Friedrich⁸  David H. O’Connor⁹ 

[1] Department of Biostatistics and Medical Informatics, School of Medicine and Public Healthy, University of Wisconsin-Madison, Madison, WI, United States;Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States;Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States;Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota-Twin Cities, St. Paul, MN, United States;Nimble Therapeutics, Inc, Madison, WI, United States;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United States;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United States;Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States;Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United States;Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, United States;Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States;

关键词: Zika virus;    ZIKV;    macaque model;    pregnancy;    maternal ZIKV infection;    congenital Zika syndrome (CZS);    maternal antibody response;   

DOI  :  10.3389/fimmu.2023.1267638

 received in 2023-07-26, accepted in 2023-09-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Krabbe, Razo, Abraham, Spanton, Shi, Bhattacharya, Bohm, Pritchard, Weiler, Mitzey, Eickhoff, Sullivan, Tan, Aliota, Friedrich, O’Connor, Golos and Mohr