Enhanced neutralization of HIV by antibodies displayed on the S-layer of Caulobacter crescentus

Antimicrob Agents Chemother. 2011 Dec;55(12):5547-52. doi: 10.1128/AAC.00509-11. Epub 2011 Sep 6.

Abstract

Innovative methods of prevention are needed to stop the more than two million new HIV-1 infections annually, particularly in women. Local application of anti-HIV antibodies has been shown to be effective at preventing infection in nonhuman primates; however, the concentrations needed are cost prohibitive. Display of antibodies on a particulate platform will likely prolong effectiveness of these anti-HIV agents and lower the cost of goods. Here, we demonstrate that the bacterium Caulobacter crescentus and its highly expressed surface-layer (S-layer) protein can provide this antibody display platform. Caulobacters displaying protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific antibodies and demonstrated functional neutralization. Compared to soluble antibodies, a neutralizing anti-HIV antibody displayed on Caulobacter was as effective or more effective at neutralizing diverse HIV-1 isolates. Moreover, when an antibody reactive with an epitope induced by CD4 binding (CD4i) was codisplayed with CD4, there was significant enhancement in HIV-1 neutralization. These results suggest that caulobacters displaying anti-HIV antibodies offer a distinct improvement in the use of antibodies as microbicides. Furthermore, these reagents can specifically evaluate anti-HIV antibodies in concert with other HIV-1 blocking agents to assess the most suitable tools for conversion to scFvs, allowing for direct display within the S-layer protein and further reducing cost of goods. In summary, C. crescentus, which can be easily produced and chemically stabilized at low cost, is well suited for engineering as an effective platform, offering an inexpensive way to produce and deliver HIV-1-specific microbicides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / immunology*
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • Caulobacter crescentus / genetics
  • Caulobacter crescentus / metabolism*
  • Drug Delivery Systems
  • Female
  • Genetic Engineering / methods
  • HIV Antibodies / immunology*
  • HIV Antibodies / isolation & purification
  • HIV Antibodies / metabolism
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Neutralization Tests
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Anti-HIV Agents
  • CD4 Antigens
  • HIV Antibodies
  • Membrane Glycoproteins
  • Recombinant Proteins
  • S-layer proteins