Sepideh Dolatshahi1, Audrey L Butler2, Mark J Siedner3,4,5, Joseph Ngonzi6, Andrea G Edlow7, Julian Adong6, Madeleine F Jennewein8, Caroline Atyeo9, Ingrid V Bassett3,4, Drucilla J Roberts10, Douglas A Lauffenburger11, Galit Alter3,9, Lisa M Bebell3,4,5. 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
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) sub-class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi-nant 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 com-promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.
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) sub-class (IgG1, 2, 3, 4) levels and antibody Fcγ receptor (FcγRn, 2a, 2b, 3a, 3b) binding profiles. We used partial least squares discrimi-nant 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 com-promised neonatal immunity. Maternal vaccination interventions may promote transfer of relevant, effective antibodies to protect HEU children against early-life infections.
Authors: F Wabwire-Mangen; R H Gray; F A Mmiro; C Ndugwa; C Abramowsky; H Wabinga; C Whalen; C Li; A J Saah Journal: J Acquir Immune Defic Syndr Date: 1999-12-01 Impact factor: 3.731
Authors: Adriana Weinberg; Marisa M Mussi-Pinhata; Qilu Yu; Rachel A Cohen; Volia C Almeida; Fabiana Amaral; Jorge Pinto; Maria L B Teixeira; Regina C M Succi; Laura Freimanis; Jennifer S Read; George Siberry Journal: AIDS Date: 2017-03-13 Impact factor: 4.177
Authors: Jessica E Atwell; Bhagvanji Thumar; Maria A Formica; Leanne J Robinson; Edward E Walsh; Christopher L King; Ruth A Karron Journal: Pediatr Infect Dis J Date: 2019-09 Impact factor: 2.129
Authors: M I de Moraes-Pinto; F Verhoeff; L Chimsuku; P J Milligan; L Wesumperuma; R L Broadhead; B J Brabin; P M Johnson; C A Hart Journal: Arch Dis Child Fetal Neonatal Ed Date: 1998-11 Impact factor: 5.747
Authors: Ken S Lau; Alwin M Juchheim; Kimberly R Cavaliere; Sarah R Philips; Douglas A Lauffenburger; Kevin M Haigis Journal: Sci Signal Date: 2011-03-22 Impact factor: 8.192
Authors: D A Schwartz; S Sungkarat; N Shaffer; J Laosakkitiboran; W Supapol; P Charoenpanich; T Chuangsuwanich; T D Mastro Journal: J Infect Dis Date: 2000-11-08 Impact factor: 5.226
Authors: Alana T Brennan; Rachael Bonawitz; Christopher J Gill; Donald M Thea; Mary Kleinman; Johanna Useem; Lindsey Garrison; Rachel Ceccarelli; Chinenye Udokwu; Lawrence Long; Matthew P Fox Journal: AIDS Date: 2016-09-24 Impact factor: 4.177
Authors: Lisa M Bebell; Joseph Ngonzi; Frederick A Meier; Chrystalle Katte Carreon; Abraham Birungi; Vanessa B Kerry; Raymond Atwine; Drucilla J Roberts Journal: Front Med (Lausanne) Date: 2022-07-08