期刊
BLOOD
卷 120, 期 23, 页码 4571-4582出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-04-422303
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资金
- Bill & Melinda Gates Foundation
- National Institutes of Health (NIH) [HHSN266200500035C, 5K08CA133521]
HIV-1 infections are generally initiated at mucosal sites. Thus, IgA antibody, which plays pivotal roles in mucosal immunity, might efficiently prevent HIV infection. However, mounting a highly effective HIV-specific mucosal IgA response by conventional immunization has been challenging and the potency of HIV-specific IgA against infection needs to be addressed in vivo. Here we show that the polymeric IgA form of anti-HIV antibody inhibits HIV mucosal transmission more effectively than the monomeric IgA or IgG1 form in a comparable range of concentrations in humanized mice. To deliver anti-HIV IgA in a continual manner, we devised a hematopoietic stem/progenitor cell (HSPC)based genetic approach using an IgA gene. We transplanted human HSPCs transduced with a lentiviral construct encoding a class-switched anti-HIV IgA (b12-IgA) into the humanized bone marrow-liver-thymus (BLT) mice. The transgene was expressed specifically in B cells and plasma cells in lymphoid organs and mucosal sites. After vaginal HIV-1 challenge, mucosal CD4(+) T cells in the b12-IgA-producing mice were protected from virus-mediated depletion. Similar results were also obtained in a second humanized model, human immune system mice. Our study demonstrates the potential of anti-HIV IgA in immunoprophylaxis in vivo, emphasizing the importance of the mucosal IgA response in defense against HIV/AIDS. (Blood.2012;120(23):4571-4582)
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