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.
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.
Eslahpazir
Jobin
J
Université Paris V and Equipe Immunité et Biothérapie Muqueuse, Unité INSERM Internationale U743 (Immunologie Humaine), Centre de Recherches des Cordeliers, Paris, France.
Jenabian
Mohammad-Ali
MA
Bouhlal
Hicham
H
Hocini
Hakim
H
Carbonneil
Cédric
C
Grésenguet
Gérard
G
Mbopi Kéou
François-Xavier
FX
LeGoff
Jérôme
J
Saïdi
Héla
H
Requena
Mary
M
Nasreddine
Nadine
N
de Dieu Longo
Jean
J
Kaveri
Srinivas V
SV
Bélec
Laurent
L
D001666:Binding Sites, Antibody / Q000276:immunology; D065100:CCR5 Receptor Antagonists; D002584:Cervix Uteri; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005260:Female; D015483:HIV Antibodies / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D014621:Vagina
D065100:CCR5 Receptor Antagonists; D015483:HIV Antibodies; D019713:Receptors, CCR5