Author:
Bialas Kristy M.,Tanaka Takayuki,Tran Dollnovan,Varner Valerie,Cisneros De La Rosa Eduardo,Chiuppesi Flavia,Wussow Felix,Kattenhorn Lisa,Macri Sheila,Kunz Erika L.,Estroff Judy A.,Kirchherr Jennifer,Yue Yujuan,Fan Qihua,Lauck Michael,O’Connor David H.,Hall Allison H. S.,Xavier Alvarez,Diamond Don J.,Barry Peter A.,Kaur Amitinder,Permar Sallie R.
Abstract
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.
Publisher
Proceedings of the National Academy of Sciences
Cited by
86 articles.
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