Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

Pollara, Justin

McGuire, Erin

Fouda, Genevieve G

Rountree, Wes

Eudailey, Josh

Overman, R Glenn

Seaton, Kelly E

Deal, Aaron

Edwards, R Whitney

Tegha, Gerald

Kamwendo, Deborah

Kumwenda, Jacob

Nelson, Julie AE

Liao, Hua-Xin

Brinkley, Christie

Denny, Thomas N

Ochsenbauer, Christina

Ellington, Sascha

King, Caroline C

Jamieson, Denise J

van der Horst, Charles

Kourtis, Athena P

Tomaras, Georgia D

Ferrari, Guido

Permar, Sallie R

Silvestri, G

United States

2016-06-01T14:43:59Z

2015-10

UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

http://www.ncbi.nlm.nih.gov/pubmed/26202232

JVI.01560-15

1098-5514

https://hdl.handle.net/10161/12061

eng

American Society for Microbiology

J Virol

10.1128/JVI.01560-15

Adult

Antibodies, Neutralizing

Antibody Specificity

Antibody-Dependent Cell Cytotoxicity

Breast Feeding

Female

HIV Antibodies

HIV Infections

HIV-1

Humans

Immunity, Mucosal

Immunoglobulin A

Immunoglobulin A, Secretory

Immunoglobulin G

Infant

Infant, Newborn

Infectious Disease Transmission, Vertical

Malawi

Milk, Human

Models, Immunological

Pregnancy

Pregnancy Complications, Infectious

Risk Factors

Young Adult

env Gene Products, Human Immunodeficiency Virus

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

Journal article

Tomaras, Georgia D|0000-0001-8076-1931

Ferrari, Guido|0000-0001-7747-3349

http://www.ncbi.nlm.nih.gov/pubmed/26202232

9952

9961

19

Basic Science Departments

Clinical Science Departments

Duke

Duke Human Vaccine Institute

Global Health Institute

Immunology

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Duke Human Vaccine Institute

Molecular Genetics and Microbiology

Pediatrics

Pediatrics, Infectious Diseases

School of Medicine

Staff

Surgery

Surgery, Surgical Sciences

University Institutes and Centers

Published

89