Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission
| Autor: | Eduardo Cisneros De La Rosa, Lisa M. Kattenhorn, Erika L. Kunz, Yujuan Yue, Don J. Diamond, Kristy M. Bialas, Michael Lauck, Peter A. Barry, Allison Hall, Jennifer L. Kirchherr, Takayuki Tanaka, Sallie R. Permar, Amitinder Kaur, Dollnovan Tran, Felix Wussow, Alvarez Xavier, David H. O’Connor, Sheila Cummings Sm Macri, Judy A. Estroff, Qihua Fan, Valerie Varner, Flavia Chiuppesi |
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| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Amniotic fluid congenital cytomegalovirus Infectious Disease Transmission Reproductive health and childbirth Antibodies Viral T-cell immunity Pregnancy Vertical Viral Maternal-Fetal Exchange Pediatric Multidisciplinary biology rhesus model neutralizing antibody virus diseases Rhesus macaque Infectious Diseases embryonic structures Cytomegalovirus Infections Female Antibody Infection Viral load Biotechnology Congenital cytomegalovirus infection Viremia Antibodies Article Vaccine Related Immune system Immunity medicine Animals Conditions Affecting the Embryonic and Fetal Periods rhesus CMV Animal Prevention Perinatal Period - Conditions Originating in Perinatal Period medicine.disease biology.organism_classification Virology Macaca mulatta Infectious Disease Transmission Vertical Disease Models Animal Good Health and Well Being Immunology Disease Models biology.protein Immunization |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 112, iss 44 |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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