Effector Function Activities of a Panel of Mutants of a Broadly Neutralizing Antibody against Human Immunodeficiency Virus Type 1

  • Hessell A
  • Poignard P
  • Hunter M
 et al. 
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Abstract

During mucosal HIV transmission, immature dendritic cells (DCs) present in the mucosa are among the first cellular targets of the virus. Previous studies have analyzed the inhibition of HIV-1 transfer from human mature DCs to T lymphocytes by neutralizing IgG, but so far no in vitro data regarding the capacity of antibodies to inhibit HIV-1 infection of immature DCs have been reported. Here, we found an increased HIV-inhibitory activity of monoclonal IgG and purified polyclonal IgG when immature monocyte-derived dendritic cells (iMDDCs) were used as target cells instead of autologous blood lymphocytes. We showed that FcgammaRII is involved in the mechanism for inhibiting HIV-1 infection of iMDDCs by IgG, whereas no induction of maturation was detected at concentrations of IgG that result in a 90% reduction of HIV replication. After induction of FcgammaRI expression on iMDDCs by IFN-gamma, an augmentation of the HIV-inhibitory activity of IgG, related to the expression of FcgammaRI, was observed. Taken together, our results demonstrate the participation of FcgammaRs in HIV-1 inhibition by IgG when iMDDCs are the targets. We propose that IgG is able to efficiently inhibit HIV-1 replication in iMDDCs and should be one of the components to be induced by vaccination.

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  • 13
  • 197-207
  • 2
  • 2013
  • 301 university boulevard
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  • AIDS Vaccines: administration & dosage
  • AIDS Vaccines: adverse effects
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  • Acquired Immunodeficiency Syndrome
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Authors

  • Ann N N J Hessell

  • Pascal Poignard

  • Meredith Hunter

  • Lars Hangartner

  • David M Tehrani

  • Wim K Bleeker

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