Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission.

Published

Journal Article

Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4(+) T-cell depleted at the time of inoculation. Animals that received the CD4(+) T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8(+) T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4(+) T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.

Full Text

Duke Authors

Cited Authors

  • Bialas, KM; Tanaka, T; Tran, D; Varner, V; Cisneros De La Rosa, E; Chiuppesi, F; Wussow, F; Kattenhorn, L; Macri, S; Kunz, EL; Estroff, JA; Kirchherr, J; Yue, Y; Fan, Q; Lauck, M; O'Connor, DH; Hall, AHS; Xavier, A; Diamond, DJ; Barry, PA; Kaur, A; Permar, SR

Published Date

  • November 2015

Published In

Volume / Issue

  • 112 / 44

Start / End Page

  • 13645 - 13650

PubMed ID

  • 26483473

Pubmed Central ID

  • 26483473

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1511526112

Language

  • eng