Plasmablast response to primary rhesus cytomegalovirus (CMV) infection in a monkey model of congenital CMV transmission

Qihua Fan, Cody S. Nelson, Kristy M. Bialas, Flavia Chiuppesi, Joshua Amos, Thaddeus C. Gurley, Dawn Jones Marshall, Joshua Eudailey, Holly Heimsath, Jonathon Himes, Ashlesha Deshpande, Mark R. Walter, Felix Wussow, Don J. Diamond, Peter A Barry, M. Anthony Moody, Amitinder Kaur, Sallie R. Permar

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4+ T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant. Compared to the CD4+ T cell-depleted dam that experienced fetal loss, the immunocompetent, nontransmitting dam had a more rapid and robust plasmablast response that produced a high proportion of RhCMVreactive antibodies, including the first identified monoclonal antibody specific for soluble and membrane-associated RhCMV envelope glycoprotein B (gB). Additionally, we noted that plasmablast RhCMV-specific antibodies had variable gene usage and maturation similar to those observed in a monkey chronically coinfected with simian immunodeficiency virus (SIV) and RhCMV. This study reveals characteristics of the early maternal RhCMV-specific humoral immune responses to primary RhCMV infection in rhesus monkeys and may contribute to a future understanding of what antibody responses should be targeted by a vaccine to eliminate congenital HCMV transmission. Furthermore, the identification of an RhCMV gB-specific monoclonal antibody underscores the possibility of modeling future HCMV vaccine strategies in this nonhuman primate model.

Original languageEnglish (US)
Article numbere00510
JournalClinical and Vaccine Immunology
Volume24
Issue number5
DOIs
StatePublished - May 1 2017

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Keywords

  • Congenital cytomegalovirus
  • Nonhuman primates
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

Fan, Q., Nelson, C. S., Bialas, K. M., Chiuppesi, F., Amos, J., Gurley, T. C., Marshall, D. J., Eudailey, J., Heimsath, H., Himes, J., Deshpande, A., Walter, M. R., Wussow, F., Diamond, D. J., Barry, P. A., Moody, M. A., Kaur, A., & Permar, S. R. (2017). Plasmablast response to primary rhesus cytomegalovirus (CMV) infection in a monkey model of congenital CMV transmission. Clinical and Vaccine Immunology, 24(5), [e00510]. https://doi.org/10.1128/CVI.00510-16