HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies.

Fouda, GG

Yates, NL

Pollara, J

Shen, X

Overman, GR

Mahlokozera, T

Wilks, AB

Kang, HH

Salazar-Gonzalez, JF

Salazar, MG

Kalilani, L

Meshnick, SR

Hahn, BH

Shaw, GM

Lovingood, RV

Denny, TN

Haynes, B

Letvin, NL

Ferrari, G

Montefiori, DC

Tomaras, GD

Permar, SR

Immunology, the Center for HIVAIDS Vaccine

United States

2017-06-02T12:45:06Z

2017-06-02T12:45:06Z

2011-09

Despite months of mucosal virus exposure, the majority of breastfed infants born to HIV-infected mothers do not become infected, raising the possibility that immune factors in milk inhibit mucosal transmission of HIV. HIV Envelope (Env)-specific antibodies are present in the milk of HIV-infected mothers, but little is known about their virus-specific functions. In this study, HIV Env-specific antibody binding, autologous and heterologous virus neutralization, and antibody-dependent cell cytotoxicity (ADCC) responses were measured in the milk and plasma of 41 HIV-infected lactating women. Although IgA is the predominant antibody isotype in milk, HIV Env-specific IgG responses were higher in magnitude than HIV Env-specific IgA responses in milk. The concentrations of anti-HIV gp120 IgG in milk and plasma were directly correlated (r = 0.75; P < 0.0001), yet the response in milk was 2 logarithm units lower than in plasma. Similarly, heterologous virus neutralization (r = 0.39; P = 0.010) and ADCC activity (r = 0.64; P < 0.0001) in milk were directly correlated with that in the systemic compartment but were 2 log units lower in magnitude. Autologous neutralization was rarely detected in milk. Milk heterologous virus neutralization titers correlated with HIV gp120 Env-binding IgG responses but not with IgA responses (r = 0.71 and P < 0.0001, and r = 0.17 and P = 0.30). Moreover, IgGs purified from milk and plasma had equal neutralizing potencies against a tier 1 virus (r = 0.65; P < 0.0001), whereas only 1 out of 35 tested non-IgG milk fractions had detectable neutralization. These results suggest that plasma-derived IgG antibodies mediate the majority of the low-level HIV neutralization and ADCC activity in breast milk.

https://www.ncbi.nlm.nih.gov/pubmed/21734046

JVI.05174-11

1098-5514

https://hdl.handle.net/10161/14737

eng

American Society for Microbiology

J Virol

10.1128/JVI.05174-11

Antibodies, Neutralizing

Antibody Formation

Antibody-Dependent Cell Cytotoxicity

Cross Reactions

Female

HIV Antibodies

HIV Infections

Humans

Immunoglobulin A

Immunoglobulin G

Milk, Human

Neutralization Tests

Plasma

env Gene Products, Human Immunodeficiency Virus

HIV-specific functional antibody responses in breast milk mirror those in plasma and are primarily mediated by IgG antibodies.

Journal article

Shen, X|0000-0001-8076-1931|0000-0002-8387-3952

Ferrari, G|0000-0001-7747-3349

Montefiori, DC|0000-0003-0856-6319

Tomaras, GD|0000-0001-8076-1931

https://www.ncbi.nlm.nih.gov/pubmed/21734046

9555

9567

18

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Human Vaccine Institute

Immunology

Institutes and Centers

Medicine

Medicine, Duke Human Vaccine Institute

Molecular Genetics and Microbiology

Pediatrics

Pediatrics, Infectious Diseases

School of Medicine

Surgery

Surgery, Surgical Sciences

Published

85