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.