Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda

Jana M. Palaia; Michelle McConnell; Jenna E. Achenbach; Claire E. Gustafson; Kristina A. Stoermer; Monica Nolan; Laura A. Guay; Thomas K. Leitner; Flavia Matovu; Allan W. Taylor; Mary Glenn Fowler; Edward N. Janoff

doi:10.1016/j.jinf.2013.11.002

Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda

Jana M. Palaia, Michelle McConnell, Jenna E. Achenbach, Claire E. Gustafson, Kristina A. Stoermer, Monica Nolan, Laura A. Guay, Thomas K. Leitner, Flavia Matovu, Allan W. Taylor, Mary Glenn Fowler, Edward N. Janoff

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Objectives: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. Results: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n=5), not IgA, diminished neutralization (mean 78±33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.

Original language	English (US)
Pages (from-to)	264-272
Number of pages	9
Journal	Journal of Infection
Volume	68
Issue number	3
DOIs	https://doi.org/10.1016/j.jinf.2013.11.002
State	Published - Mar 2014
Externally published	Yes

Bibliographical note

Funding Information:
This work supported by NIH R01-HD059527 , R01-AI41361 , R01 AI097265 , the United States Centers for Disease Control (CDC; “Pathobiology of Breast Milk among HIV-1 infected Ugandan women receiving intrapartum nevirapine” study), the Elisabeth Glaser Pediatric AIDS Foundation (EGPAF) MV-00-9-900-01432-0-00, University of Colorado Denver's Office of Interdisciplinary Women's Health Research Grant , the Mucosal and Vaccine Research Colorado Program (MAVRC) and the University of Colorado Cancer Center DNA Sequencing and Analysis Core (Grant #P30 CA046934 ). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the United States Centers for Disease Control and Prevention. We thank Jacinta Cooper for technical support and advice and the women in Kampala, Uganda for their participation.

Keywords

Breast milk
HIV
IgG, IgA
Mucosal immunity
Neutralization
Subtype A
Subtype D
Uganda

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jinf.2013.11.002

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@article{07c86086b8794ca79296efcd1ec9023a,

title = "Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda",

abstract = "Objectives: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. Results: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n=5), not IgA, diminished neutralization (mean 78±33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.",

keywords = "Breast milk, HIV, IgG, IgA, Mucosal immunity, Neutralization, Subtype A, Subtype D, Uganda",

author = "Palaia, {Jana M.} and Michelle McConnell and Achenbach, {Jenna E.} and Gustafson, {Claire E.} and Stoermer, {Kristina A.} and Monica Nolan and Guay, {Laura A.} and Leitner, {Thomas K.} and Flavia Matovu and Taylor, {Allan W.} and Fowler, {Mary Glenn} and Janoff, {Edward N.}",

note = "Funding Information: This work supported by NIH R01-HD059527 , R01-AI41361 , R01 AI097265 , the United States Centers for Disease Control (CDC; “Pathobiology of Breast Milk among HIV-1 infected Ugandan women receiving intrapartum nevirapine” study), the Elisabeth Glaser Pediatric AIDS Foundation (EGPAF) MV-00-9-900-01432-0-00, University of Colorado Denver's Office of Interdisciplinary Women's Health Research Grant , the Mucosal and Vaccine Research Colorado Program (MAVRC) and the University of Colorado Cancer Center DNA Sequencing and Analysis Core (Grant #P30 CA046934 ). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the United States Centers for Disease Control and Prevention. We thank Jacinta Cooper for technical support and advice and the women in Kampala, Uganda for their participation. ",

year = "2014",

month = mar,

doi = "10.1016/j.jinf.2013.11.002",

language = "English (US)",

volume = "68",

pages = "264--272",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders Ltd",

number = "3",

}

TY - JOUR

T1 - Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda

AU - Palaia, Jana M.

AU - McConnell, Michelle

AU - Achenbach, Jenna E.

AU - Gustafson, Claire E.

AU - Stoermer, Kristina A.

AU - Nolan, Monica

AU - Guay, Laura A.

AU - Leitner, Thomas K.

AU - Matovu, Flavia

AU - Taylor, Allan W.

AU - Fowler, Mary Glenn

AU - Janoff, Edward N.

N1 - Funding Information: This work supported by NIH R01-HD059527 , R01-AI41361 , R01 AI097265 , the United States Centers for Disease Control (CDC; “Pathobiology of Breast Milk among HIV-1 infected Ugandan women receiving intrapartum nevirapine” study), the Elisabeth Glaser Pediatric AIDS Foundation (EGPAF) MV-00-9-900-01432-0-00, University of Colorado Denver's Office of Interdisciplinary Women's Health Research Grant , the Mucosal and Vaccine Research Colorado Program (MAVRC) and the University of Colorado Cancer Center DNA Sequencing and Analysis Core (Grant #P30 CA046934 ). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the United States Centers for Disease Control and Prevention. We thank Jacinta Cooper for technical support and advice and the women in Kampala, Uganda for their participation.

PY - 2014/3

Y1 - 2014/3

N2 - Objectives: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. Results: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n=5), not IgA, diminished neutralization (mean 78±33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.

AB - Objectives: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. Methods: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. Results: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n=5), not IgA, diminished neutralization (mean 78±33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. Conclusions: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.

KW - Breast milk

KW - HIV

KW - IgG, IgA

KW - Mucosal immunity

KW - Neutralization

KW - Subtype A

KW - Subtype D

KW - Uganda

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SN - 0163-4453

VL - 68

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JO - Journal of Infection

JF - Journal of Infection

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ER -

Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda

Abstract

Bibliographical note

Keywords

UN SDGs

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