title: Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission.
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 RhCMV-reactive 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.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Cody S
authors.initials: CS
authors.lastname: Nelson
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Bialas
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, California, USA.
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiuppesi
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Amos
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Thaddeus C
authors.initials: TC
authors.lastname: Gurley
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Dawn Jones
authors.initials: DJ
authors.lastname: Marshall
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Eudailey
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Heimsath
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Himes
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Ashlesha
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Walter
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, California, USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Wussow
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, California, USA.
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.affiliation: Center for Comparative Medicine, Department of Pathology and Laboratory Medicine, University of California, Davis, California, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Barry
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA.
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA sallie.permar@dm.duke.edu.
authors.forename: Sallie R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D000818:Animals; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000151:congenital / Q000276:immunology* / Q000635:transmission*; D004195:Disease Models, Animal; D005260:Female; D018445:Infectious Disease Transmission, Vertical; D008253:Macaca mulatta; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*
keywords: congenital cytomegalovirus; nonhuman primates; vaccine