Altered Maternal Antibody Profiles in Women With Human Immunodeficiency Virus Drive Changes in Transplacental Antibody Transfer

Author:

Dolatshahi Sepideh1,Butler Audrey L2,Siedner Mark J345,Ngonzi Joseph6,Edlow Andrea G7,Adong Julian6,Jennewein Madeleine F8,Atyeo Caroline9,Bassett Ingrid V34,Roberts Drucilla J10,Lauffenburger Douglas A11,Alter Galit39ORCID,Bebell Lisa M345ORCID

Affiliation:

1. Department of Biomedical Engineering, University of Virginia , Charlottesville, Virginia , USA

2. State University of New York Upstate Medical University , Syracuse, New York , USA

3. Division of Infectious Diseases, Massachusetts General Hospital , Boston, Massachusetts , USA

4. Medical Practice Evaluation Center, Massachusetts General Hospital , Boston, Massachusetts , USA

5. Center for Global Health, Massachusetts General Hospital , Boston, Massachusetts , USA

6. Mbarara University of Science and Technology , Mbarara , Uganda

7. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital , Boston, Massachusetts , USA

8. Fred Hutchinson Cancer Center , Seattle, Washington , USA

9. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard , Cambridge, Massachusetts , USA

10. Department of Pathology, Massachusetts General Hospital , Boston, Massachusetts , USA

11. Massachusetts Institute of Technology , Cambridge, Massachusetts , USA

Abstract

Abstract Background Human immunodeficiency virus (HIV)–exposed, uninfected (HEU) children have a higher risk of severe infection, but the causes are poorly understood. Emerging data point to altered antibody transfer in women with HIV (WHIV); however, specific perturbations and the influence of antiretroviral therapy (ART) and HIV viremia remain unclear. Methods We evaluated antigen-specific transplacental antibody transfer across 14 antigens in paired maternal and umbilical cord plasma from 352 Ugandan women; 176 were WHIV taking ART. We measured antigen-specific immunoglobulin G (IgG) sub­class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi­nant analysis to define antigen-specific transplacental antibody transfer features. Results Global antibody transfer patterns were similar by maternal HIV serostatus, pointing to effective placental function in WHIV. However, HEU umbilical cord antibody profiles were altered, driven by perturbed WHIV seroprofiles, with higher levels of herpesvirus antibodies (P < .01 for Epstein-Barr virus, herpes simplex virus) and lower levels of classic vaccine-induced antibodies (P < .01 for tetanus, polio, Haemophilus influenzae type b), suggesting that umbilical cord antibody profile differences arise from imbalanced WHIV immunity. Abnormal WHIV antibody profiles were associated with HIV viremia, lower CD4 count, and postconception ART initiation (P = .01). Conclusions Perturbed immune-dominance profiles in WHIV shift the balance of immunity delivered to neonates. Perturbed HIV-associated maternal antibody profiles are a key determinant of com­promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.

Funder

Harvard University Center for AIDS Research

Harvard Clinical and Translational Science Center

Charles H. Hood Foundation

National Institute of Allergy and Infectious Diseases

National Institutes of Health

Massachusetts General Hospital

American Society of Tropical Medicine and Hygiene

Bill & Melinda Gates Foundation

Musk Foundation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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