Post-exposure prophylaxis with Zika specific human immune globulin eliminates Zika viremia in pregnant rhesus macaques
D. M. Dudley1, M. Koenig1, L. M. Stewart1, M. R. Semler1, M. Schotzko2, S. Kohn3, H. Qiu4, W. Guo5, M. Dennis5, M. T. Aliota6, S. Kodihalli4, S. R. Permar5, and D. H. O'Connor1. 1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 2Wisconsin National Primate Research Center, UW-Madison, 3Department of Radiology, UW-Madison, 4Emergent BioSolutions Canada Inc., 5Department of Pediatrics and Human Vaccine Institute, Duke University Medical Center, 6Department of Veterinary and Biomedical Sciences, University of Minnesota
Zika virus (ZIKV) continues to pose a threat to pregnancies causing fetal loss and congenital Zika syndrome with no available treatment. Human immune globulin (HIG) is a safe, effective treatment approved for use in pregnant women for a variety of viral infections. We hypothesized that immune globulin (IG) treatment derived from the serum of ZIKV-exposed individuals (ZIKV-IG) would reduce maternal viral loads and prevent adverse pregnancy/fetal outcomes. We infected 6 pregnant rhesus macaques with ZIKV-PR at gestational day 45 and treated 3 animals with Emergent's human-derived ZIKV-IG and 3 animals with non-specific IG (NS-IG) at 1 and 5 days post-infection (dpi). All animals treated with ZIKV-IG had detectable virus in plasma prior to the first ZIKV-IG administration at 1 dpi. Virus was undetectable in all treated animals by 2 dpi. This rapid control is unprecedented in pregnant macaques infected with ZIKV. One animal treated with ZIKV-IG experienced viral recrudescence at 41 dpi and remained viremic through 48 dpi. Animals treated with NS-IG had detectable virus in the plasma by 1 or 2 dpi and remained viremic for 5-13 days after which the virus was no longer detectable. ZIKV neutralizing antibodies were detected in the first ZIKV-IG treated animal by 1 hr post-infusion and were still detectable by 27 dpi. Preliminary antibody concentrations measured by whole virion binding ELISA showed the estimated half-life of the human-derived ZIKV-IG ranged from 2-10 days and detected a macaque-specific de novo antibody response starting at 20 dpi in the first ZIKV-IG treated animal. These studies are ongoing but suggest that ZIKV-IG can dramatically reduce maternal plasma viremia upon administration. Future work will assess the impact of this treatment on fetal outcomes in these pregnancies.
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