Back to Search
Start Over
A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 14, Proceedings of the National Academy of Sciences of the United States of America
- Publication Year :
- 2020
- Publisher :
- eScholarship, University of California, 2020.
-
Abstract
- Significance Zika virus (ZIKV) infection during pregnancy can cause fetal abnormalities. Vaccines against ZIKV are under development, but because of potential safety concerns due to disease-enhancing antibodies, and the time required by active immunization to induce protective antibodies, there is a need to explore alternative strategies. Recombinant monoclonal antibodies can be modified to prevent enhancement of infection, and thus could be an efficacious and safe alternative to vaccines to confer rapid protection. We show that prophylactic administration of two engineered antibodies, Z004 and Z021, to pregnant macaques partially protects against fetal neurologic damage and limits vertical transmission of ZIKV.<br />Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement (ADE) in vitro and extend their half-lives. Here we report on prophylactic coadministration of the Fc-modified antibodies to pregnant rhesus macaques challenged three times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission, protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV.
- Subjects :
- congenital Zika syndrome
Medical Sciences
Infectious Disease Transmission
Reproductive health and childbirth
Active immunization
Protein Engineering
Zika virus
Fc domain modifications
0302 clinical medicine
Pregnancy
Monoclonal
Vertical
Viral
Pregnancy Complications, Infectious
Neutralizing
Pediatric
0303 health sciences
Multidisciplinary
biology
Zika Virus Infection
Infectious
Antibodies, Monoclonal
Biological Sciences
Recombinant Proteins
3. Good health
Combination
RNA, Viral
HIV/AIDS
Drug Therapy, Combination
Female
Antibody
Infection
Biotechnology
medicine.drug_class
Viremia
Monoclonal antibody
Antibodies
Vaccine Related
03 medical and health sciences
macaque pregnancy model
Fetus
Drug Therapy
medicine
Animals
Humans
Antibody-dependent enhancement
antibody-dependent enhancement
030304 developmental biology
business.industry
Animal
Prevention
Perinatal Period - Conditions Originating in Perinatal Period
biology.organism_classification
medicine.disease
Newborn
Antibodies, Neutralizing
Virology
Infectious Disease Transmission, Vertical
Immunoglobulin Fc Fragments
Pregnancy Complications
Disease Models, Animal
Good Health and Well Being
HEK293 Cells
Animals, Newborn
Immunization
Immunoglobulin G
Disease Models
biology.protein
RNA
business
030217 neurology & neurosurgery
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America, vol 117, iss 14, Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....8532a9277cda828e4e1165743df99d18