Cross-clade HIV-1-specific neutralizing IgA in mucosal and systemic compartments of HIV-1-exposed, persistently seronegative subjects.
There is an urgent need for a universally effective HIV-1 vaccine, but whether a vaccine will be able to protect against HIV-1 of different clades is a significant concern. IgA from HIV-1-exposed, persistently seronegative (HEPS) subjects has been shown to neutralize HIV-1 and to block epithelial HIV-1 transcytosis, and it may target novel HIV-1 epitopes. We have tested the ability of plasma and mucosal IgA purified from HEPS subjects to neutralize HIV-1 primary isolates of different viral clades and phenotypes. IgA from two groups of HEPS subjects was tested: sex workers from Nairobi, Kenya, where clades A and D predominate, and the heterosexual partners of individuals infected by clade B virus. HIV-1-infected and low-risk uninfected individuals were included as controls. IgA purified from the blood, genital tract, and saliva of most HEPS sex workers demonstrated significant cross-clade HIV-1 neutralization, whereas a more clade-restricted pattern of neutralization was found in partners of clade B-infected individuals. IgA purified from HIV-1-infected individuals also mediated cross-clade neutralization, whereas IgA from uninfected controls lacked neutralizing activity. In conclusion, mucosal and plasma IgA from HEPS subjects neutralizes HIV-1 of different clades. This ability to induce HIV-1-specific systemic and mucosal IgA may be an important feature of an effective prophylactic HIV-1 vaccine.
Devito
Claudia
C
Department of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Claudia.Devito@impi.ki.se
Hinkula
Jorma
J
Kaul
Rupert
R
Kimani
Joshua
J
Kiama
Peter
P
Lopalco
Lucia
L
Barass
Claudia
C
Piconi
Stefania
S
Trabattoni
Daria
D
Bwayo
Job J
JJ
Plummer
Francis
F
Clerici
Mario
M
Broliden
Kristina
K
D016915:AIDS Vaccines / Q000276:immunology; D016022:Case-Control Studies; D003429:Cross Reactions; D005260:Female; D015483:HIV Antibodies / Q000378:metabolism*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D020010:Heterosexuality; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007630:Kenya; D008297:Male; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D012463:Saliva / Q000276:immunology; D011477:Sex Work; D012747:Sexual Partners
D016915:AIDS Vaccines; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D011994:Recombinant Proteins