Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection
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2021-12-07
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Abstract
Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital infection has been hindered by limited knowledge of the immune responses that protect against placental HCMV transmission in maternal primary and nonprimary infection. To identify protective antibody responses, we measured anti-HCMV IgG binding and anti-viral functions in maternal and cord blood sera from HCMV transmitting (n=41) and non- transmitting (n=40) mother-infant dyads identified via a large U.S.-based public cord blood bank. In a predefined immune correlate analysis, maternal monocyte-mediated antibody-dependent cellular phagocytosis (ADCP) and high avidity IgG binding to HCMV envelope glycoproteins were associated with decreased risk of congenital HCMV infection. Moreover, HCMV-specific IgG engagement of FcγRI and FcγRIIA, which mediate non-neutralizing antibody responses, was enhanced in non-transmitting mother-infant dyads and strongly correlated with ADCP. These findings suggest that Fc effector functions including ADCP protect against placental HCMV transmission. Taken together, our data indicate that future active and passive immunization strategies to prevent congenital HCMV infection should target Fc-mediated non-neutralizing antibody responses.
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Semmes, Eleanor, Itzayana Miller, Jennifer Jenks, Courtney Wimberly, Stella Berendam, Melissa Harnois, Helen Webster, Jillian Hurst, et al. (2021). Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection. 10.1101/2021.12.05.21267312 Retrieved from https://hdl.handle.net/10161/25708.
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Jillian Hurst
Intersections of the upper respiratory microbiome, environmental exposures, and childhood respiratory infections
Early life exposure to and colonization with microbes has a profound influence on the education of the immune system and susceptibility to viral and bacterial infections later in life. My research is focused on the influence of the upper respiratory microbiome on the development of recurrent respiratory infections, including acute otitis media (AOM), the leading cause of antibiotic prescriptions and healthcare consultations among children. Importantly, some children develop recurrent infections that are thought to be linked to dysbiosis of the nasopharyngeal microbiome. My overarching goals are to identify alterations in the upper respiratory microbiome associated with AOM and to elucidate host factors and exposures that predispose some children to the development of recurrent AOM episodes.
Children's Health & Discovery Initiative:
The prenatal period, infancy, childhood, and adolescence, represent critical time periods of human development that include more developmental milestones than any other period of the lifespan. Conditions during these developmental windows – including biological, social, economic, health, and environmental factors – have a profound impact on lifelong health. The Children’s Health and Discovery Initiative (CHDI) was founded on the hypothesis that interventions early in life will improve population health across the lifespan. To this end, the overarching goal of the CHDI is to create a robust coalition of multidisciplinary investigators and a pipeline of infrastructure, data, and research projects focused on developing innovative approaches to identifying and modulating early life factors that impact lifelong health and well-being.
Kyle Walsh
Dr. Walsh is Associate Professor of Neurosurgery and Pathology, Director of the Division of Neuro-epidemiology, and a Senior Fellow in the Duke Center for the Study of Aging and Human Development. He leads Duke’s Neuro-epidemiology Lab, which integrates bench science with statistical methods to study the neurobiology of glial senescence and gliomagenesis. This research interrogates human genomic and epigenomic profiles to identify both heritable and modifiable factors that contribute to neurologic and physical decline, applying these approaches to studying the shared neurobiology of cognition, glial senescence, and gliomagenesis. The lab has a long history studying telomere maintenance in pre-malignant cells and its role in the development of cancer, most notably glioblastoma.
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