Dataset Information

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.

SUBMITTER: Palaia JM

PROVIDER: S-EPMC6355459 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Palaia Jana M JM McConnell Michelle M Achenbach Jenna E JE Gustafson Claire E CE Stoermer Kristina A KA Nolan Monica M Guay Laura A LA Leitner Thomas K TK Matovu Flavia F Taylor Allan W AW Fowler Mary Glenn MG Janoff Edward N EN

The Journal of infection 20131113 3

<h4>Objectives</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 24239588

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Project description:Breast milk is nutritionally and immunologically beneficial in early life but is also a potential source of infection. Little is known about breast milk microbiota of women living with HIV (WLHIV), the impact of severe immunosuppression, and the contribution to mortality of HIV-exposed infants. Here, we performed metagenomic sequencing to characterize the bacterial microbiome and DNA virome of breast milk samples at 1 month postpartum from Kenyan WLHIV who were not receiving combination antiretroviral therapy (cART), 23 women with CD4 counts of <250 and 30 women with CD4 of >500; and additionally, 19 WLHIV with infants that lived and 26 WLHIV with infants that died during the first 2 years of life were included. We found that breast milk bacterial microbiomes in this study population were highly diverse but shared a core community composed of the Streptococcaceae, Staphylococcaceae, Moraxellaceae, and Eubacteriaceae families. The breast milk virome was dominated by human cytomegalovirus (CMV) and included the bacteriophage families Myoviridae, Siphoviridae, and Podoviridae Bacterial microbiome and virome profiles and diversity were not significantly altered by HIV immunosuppression, as defined by a CD4 of <250. CMV viral load was not associated with maternal CD4 counts or infant mortality. In conclusion, we show that the core bacterial and viral communities are resilient in breast milk despite immunosuppression in WLHIV.IMPORTANCE Breastfeeding plays an important role in seeding the infant gut microbiome and mammary health. Although most studies focus on the diverse breast milk bacterial communities, little is known about the viral communities harbored in breast milk. We performed the first breast milk virome study of an HIV population. In this study cohort of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that breast milk harbors a core bacterial microbiome and a virome dominated by human cytomegalovirus. The virome and bacterial microbiome were not substantially altered by immunosuppression or associated with infant mortality. Together, these findings indicate resilience of the microbial community in breast milk compartmentalization. These findings advance out fundamental understanding of the breast milk core microbiome and virome interactions in the context of HIV disease.

Project description:BackgroundDonated breast milk is considered beneficial to vulnerable infants. Thus, Uganda launched its first human milk bank in November 2021 to provide breast milk to preterm, low birthweight and sick babies. However, there is a scarcity of information on the acceptability of donated breast milk in Uganda. The study sought to assess the acceptability of using donated breast milk and associated factors among pregnant women at a private and a public hospital in central Uganda.MethodsThis cross-sectional study enrolled pregnant women attending antenatal care at the selected hospitals between July and October 2020. All pregnant women recruited had already given birth to at least one child. Data were collected using a semi-structured questionnaire, and we recruited participants through systematic sampling. Used frequencies, percentages and means with standard deviations to summarize variables. Assessed the association between the acceptability of donated milk and selected factors by comparing their arithmetic means using a generalized linear model to allow for clustering at the health facility level. Used a normal distribution and an identity link and calculated the adjusted mean differences together with 95% CIs [generated using robust variance estimators to correct for model misspecification].ResultsA total of 244 pregnant women with a mean age of 30 (± 5.25) years were enrolled. Sixty-one-point 5% (150/244) of the women reported that they would accept donated breast milk. Higher education (adjusted mean difference, technical versus primary level: 1.33; 95% CI 0.64, 2.02), being Muslim (adjusted mean difference, Muslim versus Christian: 1.24; 95% CI 0.77, 1.70), having heard of donated breast milk banking (adjusted mean difference, ever versus never: 0.62; 95% CI 0.18, 1.06) and presence of a serious medical condition (adjusted mean difference, preference of donated milk versus other feeds in a serious medical condition: 3.96; 95% CI, 3.28, 4.64) were associated with acceptability of donated breast milk.ConclusionsThe acceptability of using donated breast milk for infant feeding was high among pregnant women. Public sensitization and education campaigns are indispensable for the acceptability of donated milk. These programs should be designed to include women with lower education levels.

Project description:The transplacental transfer of maternal IgG to the developing fetus is critical for infant protection against infectious pathogens in the first year of life. However, factors that modulate the transplacental transfer efficiency of maternal IgG that could be harnessed for maternal vaccine design remain largely undefined. HIV-infected women have impaired placental IgG transfer, yet the mechanism underlying this impaired transfer is unknown, presenting an opportunity to explore factors that contribute to the efficiency of placental IgG transfer. We measured the transplacental transfer efficiency of maternal HIV and other pathogen-specific IgG in historical U.S. (n=120) and Malawian (n=47) cohorts of HIV-infected mothers and their HIV58 exposed uninfected and HIV-infected infants. We then examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, and IgG Fc region subclass and glycan signatures and their association with transplacental transfer efficiency of maternal antigen-specific IgG. We established 3 distinct phenotypes of placental IgG transfer efficiency in HIV-infected women, including: 1) efficient transfer of the majority of antigen-specific IgG populations; 2) generally poor IgG transfer phenotype that was strongly associated with maternal CD4+ T cell counts, hypergammaglobulinemia, and frequently yielded non-protective levels of vaccine-specific IgG; and 3) variable transfer of IgG across distinct antigen specificities. Interestingly, maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcgRIIa and FcgRIIIa, IgG subclass frequency, and Fc region glycan profiles were associated with placental IgG transfer efficiency. These maternal IgG transplacental transfer determinants were distinct among different antigen-specific IgG populations. Our findings suggest that in HIV-infected women, both maternal disease progression and Fc region characteristics modulate the selective placental transfer of distinct IgG subpopulations, with implications for both the health of HIV-exposed uninfected infants and maternal vaccine design.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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