Predominate HIV1-Specific IgG Activity in Various Mucosal Compartments of HIV1-Infected Individuals

Lü, Fabien X.

doi:10.1006/clim.2000.4910

Cited by 28 publications

(4 citation statements)

References 65 publications

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“…A reduced IgA response at mucosal sites in HIV-1 infection is contrary to what is observed with mucosal responses to other pathogens but consistent with previous reports of a low HIV-1 specific binding IgA response in favor of IgG at various mucosal sites [73]–[76]. In general, low mucosal BM IgA might reflect an ability of HIV-1 to impair local immune responses as a means of evading the humoral immune system at the mucosal site.…”

Section: Discussionsupporting

confidence: 89%

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

et al. 2012

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There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS) – only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log 10 lower (compared to 0.59 log 10 lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001)and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk.

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Section: Discussionsupporting

confidence: 89%

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

et al. 2012

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“…It is conceivable that certain monomeric envelope proteins may more accurately represent particular structural aspects of the native envelope than others, regardless of envelope clade. The identification of a mucosal Env-specific IgA response as a potential correlate of reduced transmission risk is unexpected as our group (8) and others (10,11) have demonstrated that the Env-specific IgG responses are of higher magnitude than those of IgA in breast milk and are responsible for the majority of breast milk virus neutralization and ADCC. Yet mucosal IgA may function through alternative antiviral mechanisms, such as virus aggregation, mucus binding, or inhibition of epithelial cell transcytosis (43,44).…”

Section: Discussionmentioning

confidence: 90%

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

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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.

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“…In humans, IgG has been shown to be the dominant immunoglobulin isotype in the vaginal tract and is transported across epithelial cells via the neonatal Fc Receptor (33). In addition, HIV specific IgG is predominant in vaginal secretions from infected women (34,35). In our studies we measured Gag specific IgA and IgG in rhesus macaques post HPVPsV-SIV vaccination and detected both subtypes in the vaginal tract.…”

Section: Discussionmentioning

confidence: 99%

Targeting the Vaginal Mucosa with Human Papillomavirus Pseudovirion Vaccines Delivering Simian Immunodeficiency Virus DNA

Gordon

Kines

Kutsyna

et al. 2012

The Journal of Immunology

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The majority of HIV infections occur via mucosal transmission. Vaccines that induce memory T-and B-cells in the female genital tract may prevent the establishment and systemic dissemination of HIV. We tested the immunogenicity of a vaccine that uses human papillomavirus-based gene transfer vectors, also called pseudovirions (HPV PsVs), to deliver SIV genes to the vaginal epithelium. Our findings demonstrate that this vaccine platform induces gene expression in the genital tract in both cynomolgus and rhesus macaques. Intravaginal vaccination with HPV16, HPV45, and HPV58 PsVs delivering SIV Gag DNA, induced Gag-specific antibodies in serum and the vaginal tract and T-cell responses in blood, vaginal mucosa, and draining lymph nodes that rapidly expanded following intravaginal exposure to SIVmac251. HPV PsV-based vehicles are immunogenic, warrant further testing as vaccine candidates for HIV, and may provide a useful model to evaluate the benefits and risks of inducing high levels of SIV-specific immune responses at mucosal sites prior to SIV infection.

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Predominate HIV1-Specific IgG Activity in Various Mucosal Compartments of HIV1-Infected Individuals

Cited by 28 publications

References 65 publications

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

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

Targeting the Vaginal Mucosa with Human Papillomavirus Pseudovirion Vaccines Delivering Simian Immunodeficiency Virus DNA

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