Inhibitory effect of HIV-specific neutralizing IgA on mucosal transmission of HIV in humanized mice

Blood. 2012 Nov 29;120(23):4571-82. doi: 10.1182/blood-2012-04-422303. Epub 2012 Oct 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Flow Cytometry
  • HEK293 Cells
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • HIV Infections / transmission
  • HIV-1 / immunology*
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Immunity, Mucosal / immunology*
  • Immunoglobulin A / genetics
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / metabolism
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Interleukin Receptor Common gamma Subunit / genetics
  • Interleukin Receptor Common gamma Subunit / immunology
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Mucous Membrane / immunology
  • Mucous Membrane / metabolism
  • Plasma Cells / immunology
  • Plasma Cells / metabolism


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Il2rg protein, mouse
  • Immunoglobulin A
  • Immunoglobulin G
  • Interleukin Receptor Common gamma Subunit