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Natural Antibodies to CCR5 from Breast Milk Block Infection of Macrophages and Dendritic Cells with Primary R5-Tropic HIV-1¹

Hicham Bouhlal^2,3,*, Vanessa Latry^2,, Mary Requena^*, Sylvie Aubry, Srinivas V. Kaveri, Michel D. Kazatchkine, Laurent Belec^* and Hakim Hocini^*

^* Institut Nationale de la Santé et de la Recherche Médicale (INSERM) U743, Equipe d’Immunité et Biothérapies Muqueuses et Université René Descartes Paris V, Institut Biomédical des Cordeliers, 15, rue de l’Ecole de Médecine, 75006 Paris, INSERM U681, Institut Biomédical des Cordeliers, 15, rue de l’Ecole de Médecine, 75006 Paris, Institut de Puériculture, Paris

In the present study, we demonstrate that breast milk of 66% and 83% of HIV-seronegative and seropositive women, respectively, contains natural Abs of the secretory IgA and IgG isotypes directed against the CCR5 coreceptor for R5-tropic strains of HIV-1. Abs to CCR5 were affinity purified on a matrix to which a synthetic peptide corresponding to the second extracellular loop of CCR5 had been coupled. The purified Abs bound to the CCR5 peptide in a dose-dependent fashion and to both native CCR5 expressed by Chinese hamster ovary cells transfected with CCR5 gene, macrophages, and immature dendritic cells. Although the avidity differed, the amount of anti-CCR5 Abs did not significantly differ between breast milk of HIV-seropositive and -seronegative women. Purified anti-CCR5 Abs inhibited up to 75% infection of macrophages and dendritic cells with HIV_BaL and HIV_JR-CSF. Our observations provide evidence for a role of natural Abs to CCR5 in breast milk in controlling transmissibility of HIV through breastfeeding.

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