Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Cody S. Nelson, Diana Vera Cruz, Dollnovan Tran, Kristy M. Bialas, Lisa Stamper, Huali Wu, Margaret Gilbert, Robert Blair, Xavier Alvarez, Hannah Itell, Meng Chen, Ashlesha Deshpande, Flavia Chiuppesi, Felix Wussow, Don J. Diamond, Nathan Vandergrift, Mark R. Walter, Peter A Barry, Michael Cohen-Wolkowiez, Katia KoelleAmitinder Kaur, Sallie R. Permar

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalJCI insight
Volume2
Issue number13
DOIs
StatePublished - Jul 6 2017

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Cytomegalovirus Infections
Haplorhini
Globulins
Antibodies
Infection
Mothers
Cytomegalovirus
Microcephaly
Aptitude
Sensorineural Hearing Loss
Viremia
Macaca
Neutralizing Antibodies
Macaca mulatta
Hearing Loss
Primates
Immunity
Fetus
Vaccines
Viruses

Keywords

  • Infectious disease
  • Vaccines

Cite this

Nelson, C. S., Cruz, D. V., Tran, D., Bialas, K. M., Stamper, L., Wu, H., ... Permar, S. R. (2017). Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys. JCI insight, 2(13). https://doi.org/10.1172/jci.insight.94002

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys. / Nelson, Cody S.; Cruz, Diana Vera; Tran, Dollnovan; Bialas, Kristy M.; Stamper, Lisa; Wu, Huali; Gilbert, Margaret; Blair, Robert; Alvarez, Xavier; Itell, Hannah; Chen, Meng; Deshpande, Ashlesha; Chiuppesi, Flavia; Wussow, Felix; Diamond, Don J.; Vandergrift, Nathan; Walter, Mark R.; Barry, Peter A; Cohen-Wolkowiez, Michael; Koelle, Katia; Kaur, Amitinder; Permar, Sallie R.

In: JCI insight, Vol. 2, No. 13, 06.07.2017.

Research output: Contribution to journalArticle

Nelson, CS, Cruz, DV, Tran, D, Bialas, KM, Stamper, L, Wu, H, Gilbert, M, Blair, R, Alvarez, X, Itell, H, Chen, M, Deshpande, A, Chiuppesi, F, Wussow, F, Diamond, DJ, Vandergrift, N, Walter, MR, Barry, PA, Cohen-Wolkowiez, M, Koelle, K, Kaur, A & Permar, SR 2017, 'Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys', JCI insight, vol. 2, no. 13. https://doi.org/10.1172/jci.insight.94002
Nelson, Cody S. ; Cruz, Diana Vera ; Tran, Dollnovan ; Bialas, Kristy M. ; Stamper, Lisa ; Wu, Huali ; Gilbert, Margaret ; Blair, Robert ; Alvarez, Xavier ; Itell, Hannah ; Chen, Meng ; Deshpande, Ashlesha ; Chiuppesi, Flavia ; Wussow, Felix ; Diamond, Don J. ; Vandergrift, Nathan ; Walter, Mark R. ; Barry, Peter A ; Cohen-Wolkowiez, Michael ; Koelle, Katia ; Kaur, Amitinder ; Permar, Sallie R. / Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys. In: JCI insight. 2017 ; Vol. 2, No. 13.
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