Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys
| Autor: | Katia Koelle, Robert V Blair, Nathan Vandergrift, Mark R. Walter, Peter A. Barry, Flavia Chiuppesi, Diana Vera Cruz, Ashlesha Deshpande, Amitinder Kaur, Margaret H. Gilbert, Lisa Stamper, Dollnovan Tran, Michael Cohen-Wolkowiez, Felix Wussow, Huali Wu, Kristy M. Bialas, Cody S. Nelson, Don J. Diamond, Sallie R. Permar, Meng Chen, Xavier Alvarez, Hannah L. Itell |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Hyperimmune globulin Human cytomegalovirus Microcephaly 030106 microbiology Viremia Virus Vaccine Related 03 medical and health sciences Immunity Medicine 030304 developmental biology Pediatric Infectious disease Vaccines 0303 health sciences biology 030306 microbiology business.industry Transmission (medicine) Prevention General Medicine Perinatal Period - Conditions Originating in Perinatal Period medicine.disease Virology 3. Good health Neonatal infection Infectious Diseases Good Health and Well Being 030104 developmental biology Viral replication Immunology biology.protein Immunization Sensorineural hearing loss Antibody Infection business Research Article |
| Zdroj: | JCI insight, vol 2, iss 13 |
| DOI: | 10.1101/127647 |
| Popis: | Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission in the setting of primary maternal infection and subsequent viremia, which is required for placental virus exposure. Pregnant, CD4+ T cell-depleted, rhesus CMV-seronegative (RhCMV-seronegative) rhesus monkeys were treated with either standardly produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV mixture. HIG passive infusion provided complete protection against fetal loss in both groups. The dose-optimized, RhCMV-neutralizing HIG additionally inhibited placental transmission of RhCMV and reduced viral replication and diversity. Our findings suggest that the presence of durable and potently neutralizing antibodies at the time of primary infection can prevent transmission of systemically replicating maternal RhCMV to the developing fetus, and therefore should be a primary target of vaccines to eliminate this neonatal infection. |
| Databáze: | OpenAIRE |
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