Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection.

Semmes, Eleanor C

Miller, Itzayana G

Wimberly, Courtney E

Phan, Caroline T

Jenks, Jennifer A

Harnois, Melissa J

Berendam, Stella J

Webster, Helen

Hurst, Jillian H

Kurtzberg, Joanne

Fouda, Genevieve G

Walsh, Kyle M

Permar, Sallie R

2022-09-13T15:37:35Z

2022-09-13T15:37:35Z

2022-08

2022-09-13T15:37:34Z

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 HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.

156827

0021-9738

1558-8238

https://hdl.handle.net/10161/25705

eng

American Society for Clinical Investigation

The Journal of clinical investigation

10.1172/jci156827

Humans

Cytomegalovirus

Herpesviridae Infections

Cytomegalovirus Infections

Immunoglobulin G

Cytomegalovirus Vaccines

Antibodies, Viral

Prospective Studies

Antibody Formation

Child

Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection.

Journal article

Harnois, Melissa J|0000-0002-5910-6198

Hurst, Jillian H|0000-0001-5079-9920

Kurtzberg, Joanne|0000-0002-3370-0703

Walsh, Kyle M|0000-0002-5879-9981

e156827

16

Duke

School of Medicine

Faculty

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Pathology

Pediatrics

Duke Cancer Institute

Institutes and Provost's Academic Units

Initiatives

Neurosurgery

Population Health Sciences

Duke Innovation & Entrepreneurship

Pediatrics, Transplant and Cellular Therapy

Regeneration Next Initiative

Pediatrics, Children's Health Discovery Institute

Published

132