Human immune globulin treatment controls Zika viremia in pregnant rhesus macaques

There are currently no approved drugs to treat Zika virus (ZIKV) infection during pregnancy. Hyperimmune globulin products such as VARIZIG and WinRho are FDA-approved to treat conditions during pregnancy such as Varicella Zoster virus infection and Rh-incompatibility. We administered ZIKV-specific human immune globulin as a treatment in pregnant rhesus macaques one day after subcutaneous ZIKV infection. All animals controlled ZIKV viremia following the treatment and generated robust levels of anti-Zika virus antibodies in their blood. No adverse fetal or infant outcomes were identified in the treated animals, yet the placebo control treated animals also did not have signs related to congenital Zika syndrome (CZS). Human immune globulin may be a viable prophylaxis and treatment option for ZIKV infection during pregnancy, however, more studies are required to fully assess the impact of this treatment to prevent CZS.

[1]  J. Kwak‐Kim,et al.  A systemic review of intravenous immunoglobulin G treatment in women with recurrent implantation failures and recurrent pregnancy losses , 2021, American journal of reproductive immunology.

[2]  D. O’Connor,et al.  Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques , 2021, bioRxiv.

[3]  D. O’Connor,et al.  African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques , 2020, bioRxiv.

[4]  Ernesto T. A. Marques,et al.  A Glimmer of Hope: Recent Updates and Future Challenges in Zika Vaccine Development , 2020, Viruses.

[5]  P. Vandeberg,et al.  Production of anti‐SARS‐CoV‐2 hyperimmune globulin from convalescent plasma , 2020, bioRxiv.

[6]  M. Halloran,et al.  Zika virus infection enhances future risk of severe dengue disease , 2020, Science.

[7]  Bikash R. Sahoo,et al.  Current Status of Zika Virus Vaccines: Successes and Challenges , 2020, Vaccines.

[8]  E. Harris,et al.  Antibody-Dependent Enhancement of Severe Disease Is Mediated by Serum Viral Load in Pediatric Dengue Virus Infections. , 2020, The Journal of infectious diseases.

[9]  T. Pierson,et al.  DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes , 2019, Science Translational Medicine.

[10]  S. Mahalingam Faculty Opinions recommendation of Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy. , 2019, Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature.

[11]  Brenna L Hughes,et al.  LB17. Randomized Trial to Prevent Congenital Cytomegalovirus (CMV) , 2019, Open Forum Infectious Diseases.

[12]  D. O’Connor,et al.  Long-Term Protection of Rhesus Macaques from Zika Virus Reinfection , 2019, Journal of Virology.

[13]  H. Qiu,et al.  Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice , 2019, Scientific Reports.

[14]  K. Walker,et al.  Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates , 2019, PloS one.

[15]  D. O’Connor,et al.  Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques , 2019, bioRxiv.

[16]  Gursewak Singh,et al.  Dengue Virus Immunity Increases Zika Virus‐Induced Damage during Pregnancy , 2019, Immunity.

[17]  P. Newton,et al.  Low Zika Virus Seroprevalence in Vientiane, Laos, 2003–2015 , 2019, The American journal of tropical medicine and hygiene.

[18]  ZIKA EPIDEMIOLOGY UPDATE , 2019 .

[19]  C. Rice,et al.  A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates. , 2018, Cell reports.

[20]  W. Hawley,et al.  Zika Virus Seropositivity in 1–4-Year-Old Children, Indonesia, 2014 , 2018, Emerging infectious diseases.

[21]  R. Rubin Addressing Barriers to Inclusion of Pregnant Women in Clinical Trials. , 2018, JAMA.

[22]  Andrew M Wollacott,et al.  Extending human IgG half-life using structure-guided design , 2018, mAbs.

[23]  D. Barouch,et al.  Zika virus vaccines , 2018, Nature Reviews Microbiology.

[24]  D. O’Connor,et al.  Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates , 2018, Nature Medicine.

[25]  D. Burton,et al.  Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques , 2018, Nature Communications.

[26]  T. Lazzarotto,et al.  Histological Analysis of Term Placentas from Hyperimmune Globulin-Treated and Untreated Mothers with Primary Cytomegalovirus Infection , 2018, Fetal Diagnosis and Therapy.

[27]  D. O’Connor,et al.  Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection , 2018, PloS one.

[28]  Gregory D. Gromowski,et al.  Durability and correlates of vaccine protection against Zika virus in rhesus monkeys , 2017, Science Translational Medicine.

[29]  G. Ebel,et al.  Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics , 2017, bioRxiv.

[30]  M. Halloran,et al.  Antibody-dependent enhancement of severe dengue disease in humans , 2017, Science.

[31]  M. Biggerstaff,et al.  Pregnancy Outcomes After Maternal Zika Virus Infection During Pregnancy — U.S. Territories, January 1, 2016–April 25, 2017 , 2017, MMWR. Morbidity and mortality weekly report.

[32]  Marie Bottomley Hartel,et al.  Vital Signs: Update on Zika Virus–Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure — U.S. Zika Pregnancy Registry, 2016 , 2017, MMWR. Morbidity and mortality weekly report.

[33]  Kevin M. Johnson,et al.  Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques , 2017, bioRxiv.

[34]  Jessica Jimenez,et al.  Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys , 2016, Science.

[35]  M. Beltramello,et al.  Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection , 2016, Science.

[36]  Sallie R. Permar,et al.  A rhesus macaque model of Asian-lineage Zika virus infection , 2016, Nature Communications.

[37]  D. O’Connor,et al.  Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques , 2016, bioRxiv.

[38]  J. Comer,et al.  Combination Therapy with Antibiotics and Anthrax Immune Globulin Intravenous (AIGIV) Is Potentially More Effective than Antibiotics Alone in Rabbit Model of Inhalational Anthrax , 2014, PloS one.

[39]  G. Koren,et al.  The role of VariZIG in pregnancy , 2013, Expert review of vaccines.

[40]  Matthew S. Lewis,et al.  Immune clearance of highly pathogenic SIV infection , 2013, Nature.

[41]  K. Yuen,et al.  Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. , 2013, Chest.

[42]  L. Ernst,et al.  Maternal Floor Infarction and Massive Perivillous Fibrin Deposition. , 2013, Surgical pathology clinics.

[43]  G. Dayan,et al.  The history of dengue outbreaks in the Americas. , 2012, The American journal of tropical medicine and hygiene.

[44]  Majidat A. Muhammad,et al.  Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease , 2012, Proceedings of the National Academy of Sciences.

[45]  Ted M Ross Dengue Virus , 2010, Clinics in Laboratory Medicine.

[46]  F. Alice,et al.  Ultrasound Imaging in Rhesus (Macaca mulatta) and Long-tailed (Macaca fascicularis) Macaques: Reproductive and Research Applications , 2005 .

[47]  S. Challacombe,et al.  Estimation of the intravascular half-lives of normal rhesus monkey IgG, IgA and IgM. , 1979, Immunology.

[48]  E. Franklin THE IMMUNE GLOBULINS. , 1963, Arthritis and rheumatism.