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Isolation of Leukocytes from Human Breast Milk for Use in an Antibody-dependent Cellular Phagocytosis Assay of HIV Targets
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Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission

Sallie R Permar, Youyi Fong, Nathan Vandergrift

    The Journal of Clinical Investigation
    |June 9, 2015
    PubMed

    Insights

    Maternal antibodies targeting the HIV-1 V3 loop may protect infants from vertical transmission. Boosting these antibodies could be a new strategy to prevent pediatric HIV-1 infections.

    Area of Science:

    • Immunology
    • Virology
    • Public Health

    Background:

    • Despite antiretroviral therapy, over 250,000 infants are infected with HIV-1 annually via mother-to-child transmission (MTCT).
    • Additional interventions are crucial to eliminate pediatric HIV-1 infections.

    Purpose of the Study:

    • To identify humoral immune markers associated with the risk of HIV-1 MTCT.
    • To explore immune responses linked to protection observed in the RV144 vaccine trial.

    Main Methods:

    • Selected 83 untreated HIV-1-transmitting mothers and 165 non-transmitting mothers from the Women and Infants Transmission Study (WITS).
    • Utilized multivariable logistic regression to analyze maternal IgG responses against the HIV-1 envelope's third variable loop (V3).
    • Assessed neutralizing antibody (Ab) responses against tier 1 HIV-1 strains and characterized V3-specific IgG monoclonal antibodies (mAbs).

    Main Results:

    • Higher magnitude of maternal IgG responses specific for the HIV-1 V3 loop predicted a reduced risk of MTCT.
    • Neutralizing Ab responses against tier 1 HIV-1 strains also predicted a lower risk of peripartum transmission.
    • Recombinant maternal V3-specific IgG mAbs demonstrated neutralization of autologous HIV-1 isolates.

    Conclusions:

    • Maternal V3-specific antibody responses are associated with a reduced risk of HIV-1 MTCT.
    • These antibodies can neutralize autologous HIV-1 strains, suggesting a protective mechanism.
    • Enhancing maternal V3-specific antibody responses may offer a novel strategy to further decrease HIV-1 MTCT.

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