1233. Cytomegalovirus-Neutralizing Antibody Responses are Associated with Protection Against Fetal Loss, but not Placental Transmission, in a Novel Rhesus Monkey Model of Congenital CMV Transmission
Session: Poster Abstract Session: Viral Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 20151004 IDweekposter.pdf (333.8 kB)
  • Background: Placental transmission of human cytomegalovirus (CMV) is a significant cause of infant hearing loss and brain damage worldwide. Strategies to reduce the rate of congenital CMV transmission include the development of a protective maternal CMV vaccine, but will first require the identification of maternal immune correlates of protection. Thus, we sought to define the role of maternal cellular and humoral immunity in congenital CMV transmission and disease in a novel nonhuman primate model of congenital CMV transmission.

    Methods: Intravenous virus inoculation of rhCMV-seronegative adult females in the early second trimester of pregnancy led to asymptomatic congenital rhCMV infection in 2 of 3 live-born infants (66%, n = 3), whereas similar inoculation of CD4+ T cell depleted, rhCMV-seronegative dams resulted in a higher congenital rhCMV transmission rate (100%, n = 5) and induced spontaneous abortion in 4 of 5 animals at week 3 post-infection.

    Results: Analysis of maternal humoral immune responses in both groups of females revealed a remarkable delay in the appearance of rhCMV-neutralizing antibodies in CD4+ T cell depleted dams, suggesting a potential role for maternal antibodies in the protection against severe congenital rhCMV disease.  To determine whether the presence of rhCMV-specific antibodies is sufficient for protection against congenital rhCMV transmission and fetal loss, we administered an intravenous dose of pooled rhesus hyperimmune globulin to 3 additional rhCMV-seronegative, CD4+ T cell depleted dams 1 hour prior to rhCMV infection at a similar gestational time point. Antibody infusion resulted in a lower rate of congenital rhCMV transmission (66%, n = 3) than was observed in the untreated CD4+ T cell depleted dams, and additionally, all 3 infants were carried to 6 weeks post rhCMV-infection without complication.

    Conclusion: Our data indicate that the rhCMV-specific neutralizing antibody responses, which are dependent on CD4+ T cell help, can reduce the severity of congenital CMV disease but do not fully protect against fetal acquisition. Continued studies to examine the impact of both distinct epitope-specific neutralizing antibodies and maternal cellular immunity will be critical to the development of a vaccine for the prevention of congenital CMV infection.

    Kristy Bialas, PhD1, Takayuki Tanaka, DVM2, Dollnovan Tran, BS3, Eduardo Cisneros De La Rosa, BS1, Lisa Kattenhorn, DVM, PhD2, Sheila Macri, DVM2, Cody Nelson, BS1, Judy Estroff, MD4, Pyone Aye, DVM/PhD3, Margaret Gilbert, DVM3, Amitinder Kaur, MD3 and Sallie Permar, MD/PhD1, (1)Duke Human Vaccine Institute, Duke University, Durham, NC, (2)New England Research Primate Center, Harvard Medical School, Southborough, MA, (3)Tulane National Primate Research Center, Tulane University, Covington, LA, (4)Boston Children's Hospital, Boston, MA

    Disclosures:

    K. Bialas, None

    T. Tanaka, None

    D. Tran, None

    E. Cisneros De La Rosa, None

    L. Kattenhorn, None

    S. Macri, None

    C. Nelson, None

    J. Estroff, None

    P. Aye, None

    M. Gilbert, None

    A. Kaur, None

    S. Permar, None

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