Cervicovaginal secretory antibodies to human immunodeficiency virus type 1 (HIV-1) that block viral transcytosis through tight epithelial barriers in highly exposed HIV-1-seronegative African women.
Antibodies to human immunodeficiency virus (HIV) of the IgA, IgG, and IgM isotypes and high levels of the HIV suppressive beta-chemokine RANTES (regulated on activation, normally T cell expressed and secreted) were found in the cervicovaginal secretions (CVSs) of 7.5% of 342 multiply and repeatedly exposed African HIV-seronegative female sex workers. The antibodies are part of a local compartmentalized secretory immune response to HIV, since they are present in vaginal fluids that are free of contaminating semen. Cervicovaginal antibodies showed a reproducible pattern of reactivity restricted to gp160 and p24. Locally produced anti-env antibodies exhibit reactivity toward the neutralizing ELDKWA epitope of gp41. Study results show that antibodies purified from CVSs block the transcytosis of cell-associated HIV through a tight epithelial monolayer in vitro. These findings suggest that genital resistance to HIV may involve HIV-specific cervicovaginal antibody responses in a minority of highly exposed HIV-seronegative women in association with other protecting factors, such as local production of HIV-suppressive chemokines.
Bélec
L
L
Unité INSERM U430, Immunopathologie Humaine, Hôpital Broussais, and Université Pierre et Marie Curie Paris VI and Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France. laurent.belec@egp.ap-hop-paris.fr
Ghys
P D
PD
Hocini
H
H
Nkengasong
J N
JN
Tranchot-Diallo
J
J
Diallo
M O
MO
Ettiègne-Traore
V
V
Maurice
C
C
Becquart
P
P
Matta
M
M
Si-Mohamed
A
A
Chomont
N
N
Coulibaly
I M
IM
Wiktor
S Z
SZ
Kazatchkine
M D
MD
D000293:Adolescent; D000328:Adult; D000349:Africa; D000918:Antibody Specificity; D001692:Biological Transport; D002460:Cell Line; D002584:Cervix Uteri / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D018604:Epitope Mapping; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology / Q000494:pharmacology*; D015488:HIV Antigens / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology / Q000494:pharmacology*; D007136:Immunoglobulins / Q000276:immunology / Q000494:pharmacology; D008875:Middle Aged; D011477:Sex Work; D014621:Vagina / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D016207:Cytokines; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D007071:Immunoglobulin A, Secretory; D007136:Immunoglobulins