#Medical #Outcomes in Women Who Became #Pregnant after #Vaccination with a #VLP Experimental #Vaccine against #Influenza A (#H1N1) 2009 Virus Tested during 2009 #Pandemic Outbreak (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Sep 17;11(9). pii: E868. doi: 10.3390/v11090868.

Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak.

Cérbulo-Vázquez A1, Arriaga-Pizano L2, Cruz-Cureño G3, Boscó-Gárate I4, Ferat-Osorio E5, Pastelin-Palacios R6, Figueroa-Damian R7, Castro-Eguiluz D8, Mancilla-Ramirez J9, Isibasi A10, López-Macías C11,12,13.

Author information: 1 Facultad de Medicina, Plan de Estudios Combinados en Medicina (MD, PhD Program), Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico. cerbulo@unam.mx. 2 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. landapi@hotmail.com. 3 Escuela Nacional de Ciencias Biológicas, Programa de Inmunología, Instituto Politécnico Nacional, Mexico City CP 11340, Mexico. gabrielacruz30@gmail.com. 4 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. ibosco45@hotmail.com. 5 Servicio de Cirugía Gastrointestinal, Unidad Médica de Alta Especialidad, Hospital de Especialidades Dr Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. eduardoferat@prodigy.net.mx. 6 Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico. rodolfop@unam.mx. 7 Departamento de Infectología, Instituto Nacional de Perinatología, Mexico City CP 11000, Mexico. rfd6102@yahoo.com.mx. 8 Consejo Nacional de Ciencia y Tecnología (CONACYT)- Departamento de Investigación Clínica, Instituto Nacional de Cancerología, Mexico City CP 14080, Mexico. angeldenisse@gmail.com. 9 Escuela Superior de Medicina, Instituto Politécnico Nacional; Hospital de la Mujer, Secretaria de Sauld, Mexico City CP 11340, Mexico. javiermancilla@hotmail.com. 10 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. isibasi@prodigy.net.mx. 11 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. constantino@sminmunologia.mx. 12 Visiting Professor of Immunology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK. constantino@sminmunologia.mx. 13 Mexican Translational Immunology Research Group, Federation of Clinical Immunology Societies Centers of Excellence, National Autonomous University of Mexico, Mexico City 04510, Mexico. constantino@sminmunologia.mx.

 

Abstract

The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 μg dose of VLP vaccine, or (3) 45 μg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants.

KEYWORDS: antibody titers; influenza A(H1N1)pdm09; pregnant women; vaccination; virus-like particle

PMID: 31533277 DOI: 10.3390/v11090868

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.

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#Postnatal #Zika virus #infection of #NHP #infants born to mothers infected with homologous #Brazilian Zika virus (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Sep 5;9(1):12802. doi: 10.1038/s41598-019-49209-7.

Postnatal Zika virus infection of nonhuman primate infants born to mothers infected with homologous Brazilian Zika virus.

Maness NJ1,2, Schouest B3,4, Singapuri A5, Dennis M6, Gilbert MH3, Bohm RP3, Schiro F3, Aye PP3, Baker K3, Van Rompay KKA5,7, Lackner AA3, Bonaldo MC8, Blair RV3, Permar SR6,9, Coffey LL5, Panganiban AT10,3, Magnani D11.

Author information: 1 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA. nmaness@tulane.edu. 2 Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA. nmaness@tulane.edu. 3 Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA. 4 Biomedical Sciences Training Program, Tulane University School of Medicine, New Orleans, Louisiana, USA. 5 Department of Pathology, Microbiology and Immunology, University of California, Davis, CA, USA. 6 Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA. 7 California National Primate Research Center, University of California, Davis, California, USA. 8 Laboratório de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil. 9 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA. 10 Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA. 11 MassBiologics of the University of Massachusetts Medical School, Boston, Massachusetts, USA.

 

Abstract

Recent data in a nonhuman primate model showed that infants postnatally infected with Zika virus (ZIKV) were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. In this pilot study, we addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding antibodies remained detectable until viral infection at 5 months. Acute serum viremia was comparatively lower than adults infected with the same Brazilian isolate of ZIKV (n = 11 pregnant females, 4 males, and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute and our study lacks an important comparison with postnatally infected infants born to naïve dams, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

PMID: 31488856 DOI: 10.1038/s41598-019-49209-7

Keywords: Zika Virus; Zika Congenital Infection; Pregnancy; Animal models.

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A Gorilla #Adenovirus-Based #Vaccine against #Zika Virus Induces Durable #Immunity and Confers #Protection in #Pregnancy (Cell Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Cell Rep. 2019 Sep 3;28(10):2634-2646.e4. doi: 10.1016/j.celrep.2019.08.005.

A Gorilla Adenovirus-Based Vaccine against Zika Virus Induces Durable Immunity and Confers Protection in Pregnancy.

Hassan AO1, Dmitriev IP2, Kashentseva EA2, Zhao H3, Brough DE4, Fremont DH5, Curiel DT2, Diamond MS6.

Author information: 1 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. 2 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA. 3 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. 4 Precigen, 20358 Seneca Meadows Parkway, Germantown, MD 20876, USA. 5 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. 6 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diamond@wusm.wustl.edu.

 

Abstract

The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD8+ T cell independent, and for GAd-Eecto requires the complement component C1q. Immunization of GAd-Zvp induces antibodies against a key neutralizing epitope on domain III of E protein and confers durable protection as evidenced by memory B and long-lived plasma cell responses and challenge studies 9 months later. In two models of ZIKV infection during pregnancy, GAd-Zvp prevents maternal-to-fetal transmission. The gorilla adenovirus-based vaccine platform encoding full-length prM and E genes is a promising candidate for preventing congenital ZIKV syndrome and possibly infection by other flaviviruses.

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

KEYWORDS: Zika virus; adaptive immunity; flavivirus; pathogenesis; pregnancy; vaccine

PMID: 31484074 DOI: 10.1016/j.celrep.2019.08.005

Keywords: Zika Virus; Vaccines; Animal models.

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Incidence of #Maternal #Sepsis and Sepsis-Related Maternal #Deaths in the #USA (JAMA, abstract)

[Source: JAMA, full page: (LINK). Abstract, edited.]

Research Letter / September 3, 2019

Incidence of Maternal Sepsis and Sepsis-Related Maternal Deaths in the United States

Matthew K. Hensley, MD, MPH1; Melissa E. Bauer, DO2; Lindsay K. Admon, MD, MSc3; et al Hallie C. Prescott, MD, MSc4

Author Affiliations: 1 Department of Internal Medicine, University of Michigan, Ann Arbor; 2 Department of Anesthesiology, University of Michigan, Ann Arbor; 3 Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor; 4 VA Center for Clinical Management Research, HSR&D Center of Innovation, Ann Arbor, Michigan

JAMA. 2019;322(9):890-892. doi:10.1001/jama.2019.9818

 

Abstract

Maternal sepsis is a leading cause of maternal morbidity and mortality. However, population-based estimates of maternal sepsis occurring after delivery hospitalization have been limited because previous studies have focused on select populations or have not followed up patients longitudinally.1,2 Thus, the burden of maternal sepsis and sepsis-related deaths may be underestimated. We assessed the nationwide incidence and outcomes of maternal sepsis within 42 days of delivery hospitalization discharge using all-payer data.

Keywords: Sepsis; Pregnancy; USA.

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#Lassa Fever in #Pregnancy with a Positive #Maternal and #Fetal Outcome: A Case Report (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2019 Aug 26. pii: S1201-9712(19)30349-2. doi: 10.1016/j.ijid.2019.08.023. [Epub ahead of print]

LASSA FEVER IN PREGNANCY WITH A POSITIVE MATERNAL AND FETAL OUTCOME: A CASE REPORT.

Agboeze J1, Nwali MI2, Nwakpakpa E2, Ogah OE2, Onoh R2, Eze J2, Ukaegbe C2, Ajayi N2, Nnadozie UU2, Orji ML2, Ojide CK2, Unigwe US2, Chika-Igwenyi N2, Nwidi UD2, Clement UC3, Kalombo C3, Makwe C3, Tshiang J3.

Author information: 1 Alex-Ekwueme University Federal Teaching Hospital Abakaliki, Ebonyi, Nigeria. Electronic address: jagboeze@gmail.com. 2 Alex-Ekwueme University Federal Teaching Hospital Abakaliki, Ebonyi, Nigeria. 3 Medecins sans Frontieres, Nigeria.

 

Abstract

BACKGROUND:

Lassa fever is a rodent-borne zoonosis that clinically manifests as an acute haemorrhagic fever. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented to date. It is treated using ribavirin.

CASE PRESENTATION:

We report a case of a 25-year old multigravida at 29weeks gestational age with fever who was initially thought to have malaria in pregnancy. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. She subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved and she made full recovery. Her close contacts showed no evidence of Lassa virus infection.

CONCLUSION:

This report adds to the body of literature that individuals may survive Lassa fever during pregnancy with good maternal and fetal outcome.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Abakaliki; Diagnosis; Lassa fever; Pregnancy; Survival

PMID: 31465848 DOI: 10.1016/j.ijid.2019.08.023

Keywords: Lassa Fever; Pregnancy; Nigeria.

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#Host and viral #mechanisms of #congenital #Zika #syndrome (Virulence, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virulence. 2019 Dec;10(1):768-775. doi: 10.1080/21505594.2019.1656503.

Host and viral mechanisms of congenital Zika syndrome.

Liang B1, Guida JP2, Costa Do Nascimento ML2, Mysorekar IU1,3,4.

Author information: 1 Department of Obstetrics and Gynecology, Washington University School of Medicine , St. Louis , MO , USA. 2 Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas , Campinas , Brazil. 3 Department of Pathology and Immunology, Washington University School of Medicine , St. Louis , MO , USA. 4 Center for Reproductive Health Sciences, Washington University School of Medicine , St. Louis , MO , USA.

 

Abstract

In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by Aedes aegypti mosquitoes, however non-vector-dependent routes are also possible. Mechanisms of maternal-fetal transmission remain unknown, and the trans-placental route has been extensively studied in animal models and in human samples. The aim of this review was to summarize recent studies that helped to elucidate the mechanism of CZS in animal models and observational studies. There are still challenges in the diagnosis and prevention of CZS in humans, due to the large gap that remains in translating ZIKV research to clinical practice. Translational research linking governments, local health workers, scientists and industry is fundamental to improve care for mothers and children.

KEYWORDS: Placenta; autophagy; hydroxychloroquine; interferon lambda; trophoblast; type I interferon

PMID: 31451049 DOI: 10.1080/21505594.2019.1656503

Keywords: Zika Virus; Zika Congenital Syndrome; Pregnancy.

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Efficient #transplacental #IgG transfer in women infected with #Zika virus during #pregnancy (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy

Tulika Singh , Cesar A. Lopez , Camila Giuberti, Maria L. Dennis, Hannah L. Itell, Holly J. Heimsath, Helen S. Webster, Hunter K. Roark, Paulo R. Merçon de Vargas, Allison Hall, Ralph G. Corey, Geeta K. Swamy, Reynaldo Dietze, Helen M. Lazear , Sallie R. Permar

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Published: August 26, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007648 / This is an uncorrected proof.

 

Abstract

Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigen-specific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics.

 

Author summary

In 2015, a Zika virus (ZIKV) epidemic emerged in Latin America, where dengue virus (DENV) already was endemic. The ZIKV epidemic revealed an array of birth defects and neurodevelopmental abnormalities in newborns associated with maternal infection. ZIKV may now be co-endemic in Latin America with DENV. Antibodies transferred from mother to the fetus in pregnancy can protect newborns from infections in early life, before they are eligible for vaccination. Conversely, flavivirus-specific IgG transfer could mediate enhancement of DENV infections in early life, or transfer ZIKV immune complexes into the fetal compartment. As a first step in evaluating these potential outcomes, it is important to understand whether ZIKV infection in pregnancy and its associated placental pathology impacts the magnitude or types of IgG subpopulations that are transferred across the placenta. To test this, we assessed paired maternal and cord blood collected at delivery from mothers who presented with rash and/or fever in pregnancy during the ZIKV epidemic in Vitoria, Brazil. Of these, we classified 8 as ZIKV-infected based on virus detection and/or neutralization serology, and 12 as ZIKV-uninfected. Comparing ZIKV-infected and uninfected groups, we detected no difference in transfer efficiency of IgG targeting ZIKV, DENV, or routine vaccine antigens. These findings indicate that the magnitude of IgG transferred across the placenta was not deficient at the time of birth in the setting of maternal ZIKV infection. Sustained transplacental transfer with ZIKV infection during pregnancy indicates that ZIKV exposure in utero should not impact maternal antibody mediated protection during early life, yet indicates potential risks of severe primary DENV infection in ZIKV-exposed infants in endemic regions, or antibody transport of ZIKV to the fetal compartment. This passive antibody transfer in pregnancy is an important consideration for flavivirus vaccine and therapeutic development efforts.

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Citation: Singh T, Lopez CA, Giuberti C, Dennis ML, Itell HL, Heimsath HJ, et al. (2019) Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy. PLoS Negl Trop Dis 13(8): e0007648. https://doi.org/10.1371/journal.pntd.0007648

Editor: Ernesto T. A. Marques, University of Pittsburgh, UNITED STATES

Received: March 3, 2019; Accepted: July 22, 2019; Published: August 26, 2019

Copyright: © 2019 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by the Duke Global Health Institute* (SRP), Duke-NUS Medical School (* (SRP), the American Society for Reproductive Medicine* (SRP), the Duke-Brazil Institute* (TS), the National Institutes of Health [R21 AI132677 to SRP; and T32 CA009111 to TS], start-up funds from the University of North Carolina Chapel Hill (HML), and Coordenaçáo de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (Finance Code 001 to CG). The pregnancy cohort in Brazil was funded by Fundação de Amparo à Pesquisa do Espírito Santo (306/2016 to RD; Protocol Financial Support Number: 74910132/16), and led by RD and S.R.P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

*These funding sources do not have a number associated with the research award.

Competing interests: TS, CAL, CG, MLD, HLI, HJH., PMV, AH, RD, HSW, HKR, and HML all certify no potential conflicts of interest. SRP is serving as a consultant for vaccine programs at Merck, Pfizer, and Moderna. GKS is on the scientific advisory board for investigational vaccine products with Saol Therapeutics and GlaxoSmithKline, the Chair of Data Safety and Monitoring Board with Pfizer, and the site PI at Duke for testing investigational vaccines and products with Novavax, Regeneron, and GlaxoSmithKline/Novartis. In the past three years, RGC has served as a consultant for Arsanis, Basilea, Bayer, Cempra, Contrafect, Meiji Seika Pharma Co., Melinta, Merck, Motif, Paratek, Parion Sciences, Quintiles, Regeneron, SCPharma, The Medicines Company, and Theravance. Moreover, RGC has served on the Adjudication Committee at Bio2 Medical and Novella, the scientific advisory board of Medtronic and Tetraphase, and on the Mortality Board of Pfizer.

Keywords: Zika Virus; Immunoglobulins; Vaccines; Pregnancy.

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