This Article Full Text Full Text (PDF) Other Versions of this Article: CVI.00463-07v1 15/5/872    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Eslahpazir, J. Articles by Bélec, L. PubMed PubMed Citation Articles by Eslahpazir, J. Articles by Bélec, L.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, May 2008, p. 872-884, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00463-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Jobin Eslahpazir,¹ Mohammad-Ali Jenabian,¹ Hicham Bouhlal,^1, Hakim Hocini,¹ Cédric Carbonneil,¹ Gérard Grésenguet,² François-Xavier Mbopi Kéou,³ Jérôme LeGoff,^1,4 Héla Saïdi,¹ Mary Requena,¹ Nadine Nasreddine,¹ Jean de Dieu Longo,² Srinivas V. Kaveri,⁵ and Laurent Bélec^1,4*

Université Paris V and Equipe Immunité et Biothérapie Muqueuse, Unité INSERM Internationale U743 (Immunologie Humaine), Centre de Recherches des Cordeliers, Paris, France,¹ 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,² Faculté des Sciences de la Santé, Université Yaoundé I, Yaoundé, Cameroon,³ Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France,⁴ Université Paris Descartes (Paris V) and Unité INSERM U681, Centre de Recherches Biomédicales des Cordeliers, Paris, France⁵

Received 23 November 2007/ Returned for modification 31 December 2007/ Accepted 13 February 2008

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.

Published ahead of print on 19 March 2008.

Present address: INSERM U925, Laboratoire d'Immunologie, Faculté de Médecine, Université Jules Verne Picardie, Amiens, France.