Human immunodeficiency virus type 1 IgA antibody in breast milk and serum

Duprat, C.; Mohammed, Zeena; Datta, Pratibha; Stackiw, W.; Ndinya-Achola, Jackoniah O.; Kreiss, Joan K.; Holmes, King K.; Plummer, Francis A.; Embreé, Joanne

doi:10.1097/00006454-199407000-00004

Cited by 34 publications

(27 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, mucosal Env-specific IgA responses have also been observed among highly exposed seronegative individuals, including female sex workers and discordant couples (45). In contrast, previous studies have not found breast milk Env-specific IgA to be associated with reduced risk of postnatal HIV-1 transmission (9,(11)(12)(13). A significant difference between our study and previous breast milk studies is that we assessed the magnitude of Env-binding IgA responses, not frequency of responders, as correlates of transmission risk.…”

Section: Discussionmentioning

confidence: 99%

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

Pollara

McGuire

Fouda

et al. 2015

J Virol

View full text Add to dashboard Cite

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. IMPORTANCEInfants 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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Pollara

McGuire

Fouda

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…Although persistence of HIV-specific IgA and IgM in breast milk was associated with reduced transmission in one study in Rwanda, 10 no protective association was observed in two other studies. 8,11 HIV-specific sIgA has been detected frequently in cervicovaginal samples from exposed but persistently uninfected cohorts of high-risk women, 12-14 suggesting a role for these mucosal responses in resistance to HIV. Purified sIgA from exposed-uninfected women has been shown to neutralize a variety of HIV subtypes and phenotypes 15,16 and to block transcytosis.…”

Section: Introductionmentioning

confidence: 99%

“…5 HIV-specific IgA antibodies are detected in breast milk of a high proportion of HIV-positive, lactating women. [6][7][8] In an in vitro model, sIgA purified from colostrum was able to block one of the pathways involved in HIV penetration across mucosa, that is, transcytosis through epithelial cells, 9 suggesting that sIgA may be related to decreased infectivity of breast milk. Although persistence of HIV-specific IgA and IgM in breast milk was associated with reduced transmission in one study in Rwanda, 10 no protective association was observed in two other studies.…”

mentioning

confidence: 99%

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Kuhn

Trabattoni

Kankasa

et al. 2006

The Journal of Pediatrics

View full text Add to dashboard Cite

Objectives-To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants.Study design-Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters).Results-HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities.Conclusions-HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.Human immunodeficiency virus (HIV) can be transmitted from an HIV-infected mother to her child through breast-feeding. This poses a serious dilemma for health policy-makers. Although complete avoidance of breast-feeding would eliminate the risk of breast-feeding-associated transmission, breast milk substitutes are unaffordable, unavailable, unacceptable, and unsafe for many HIV-infected women in low resource settings. The quantity of viral RNA and cellassociated viral DNA in breast milk from HIV-positive women strongly predicts mother-tochild transmission among breast-fed infants. [1][2][3] What is puzzling, however, is why the majority of breast-fed infants born to HIV-positive mothers remain uninfected despite prolonged exposure. Although breast milk is clearly a route of transmission, human milk is also a rich source of a multitude of innate and specific immune factors that may play a role in modulating the risk of infection. 4 Better understanding of anti-infective properties of breast milk may assist Secretory immunoglobulin A (sIgA) is the predominant immunoglobulin in breast milk and is associated with passive immunity to other (non-HIV) pathogens among breast-fed infants. 5 HIV-specific IgA antibodies are detected in breast milk of a high proportion of HIV-positive, lactating women. [6][7][8] In an in vitro model, sIgA purified from colostrum was able to block one of the pathways involved in HIV penetration across mucosa, that is, transcytosis through epithelial cells, 9 suggesting that sIgA may be related to decreased infectivity of breast milk. Although persistence of HIV-specific IgA and IgM in breast milk was associated with reduced transmission in one study in Rwanda, 10 no protective association was observed in two other studies. 8,11 HIV-specific sIgA has been detected frequently in cervicovaginal samples from exposed but persistently uninfected cohorts of high-risk women, 12-14 suggesting a role for these mucosal responses in resistance to HIV. Purified sIgA from ex...

show abstract

“…As breast milk contains a large amount of IgG and IgA antibodies, it has been suggested that protection is mediated by mucosal IgG and IgA responses that are effective in blocking mucosal HIV transmission. HIV Envelope (Env)-specific antibodies have been identified in the milk of HIV-infected, lactating women, but the magnitude of these responses are similar in postnatal transmitting and nontransmitting HIV-infected mothers (9)(10)(11). Likewise, simian immunodeficiency virus (SIV) Env-specific antibody responses in the milk of SIV-infected, lactating rhesus macaques (RhMs) are similar in magnitude between animals that did and did not transmit the virus through breastfeeding (12).…”

mentioning

confidence: 99%

Lack of B Cell Dysfunction Is Associated with Functional, gp120-Dominant Antibody Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys

Amos

Wilks

Fouda

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

Human immunodeficiency virus type 1 IgA antibody in breast milk and serum

Cited by 34 publications

References 0 publications

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

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

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Lack of B Cell Dysfunction Is Associated with Functional, gp120-Dominant Antibody Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys

Contact Info

Product

Resources

About