Infection of Macrophages and Dendritic Cells with Primary R5-Tropic Human Immunodeficiency Virus Type 1 Inhibited by Natural Polyreactive Anti-CCR5 Antibodies Purified from Cervicovaginal Secretions

Author:

Eslahpazir Jobin12345,Jenabian Mohammad-Ali12345,Bouhlal Hicham12345,Hocini Hakim12345,Carbonneil Cédric12345,Grésenguet Gérard12345,Kéou François-Xavier Mbopi12345,LeGoff Jérôme12345,Saïdi Héla12345,Requena Mary12345,Nasreddine Nadine12345,de Dieu Longo Jean12345,Kaveri Srinivas V.12345,Bélec Laurent12345

Affiliation:

1. Université Paris V and Equipe Immunité et Biothérapie Muqueuse, Unité INSERM Internationale U743 (Immunologie Humaine), Centre de Recherches des Cordeliers, Paris, France

2. Centre National de Référence des Maladies Sexuellement Transmissibles et du SIDA and Unité d'Intervention et de Recherches sur les Maladies Sexuellement Transmissibles et le SIDA, Faculté des Sciences de la Santé, Bangui, Central African Republic

3. Faculté des Sciences de la Santé, Université Yaoundé I, Yaoundé, Cameroon

4. Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France

5. Université Paris Descartes (Paris V) and Unité INSERM U681, Centre de Recherches Biomédicales des Cordeliers, Paris, France

Abstract

ABSTRACT Heterosexual contact is the primary mode of human immunodeficiency virus (HIV) type 1 (HIV-1) transmission worldwide. The chemokine receptor CCR5 is the major coreceptor that is associated with the mucosal transmission of R5-tropic HIV-1 during sexual intercourse. The CCR5 molecule is thus a target for antibody-based therapeutic strategies aimed at blocking HIV-1 entry into cells. We have previously demonstrated that polyreactive natural antibodies (NAbs) from therapeutic preparations of immunoglobulin G and from human breast milk contain NAbs directed against CCR5. Such antibodies inhibit the infection of human macrophages and T lymphocytes by R5-tropic isolates of HIV in vitro. In the present study, we demonstrate that human immunoglobulins from the cervicovaginal secretions of HIV-seronegative or HIV-seropositive women contain NAbs directed against the HIV-1 coreceptor CCR5. Natural affinity-purified anti-CCR5 antibodies bound to CCR5 expressed on macrophages and dendritic cells and further inhibited the infection of macrophages and dendritic cells with primary and laboratory-adapted R5-tropic HIV but not with X4-tropic HIV. Natural anti-CCR5 antibodies moderately inhibited R5-tropic HIV transfer from monocyte-derived dendritic cells to autologous T cells. Our results suggest that mucosal anti-CCR5 antibodies from healthy immunocompetent donors may hamper the penetration of HIV and may be suitable for use in the development of novel passive immunotherapy regimens in specific clinical settings of HIV infection.

Publisher

American Society for Microbiology

Subject

Microbiology (medical),Clinical Biochemistry,Immunology,Immunology and Allergy

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