Enhanced Neutralization of HIV by Antibodies Displayed on the S-Layer of Caulobacter crescentus
| Autor: | John Smit, Marc S. Horwitz, John F. Nomellini, Christopher J. Lewis, Mark Duval, Lisa A. Cavacini |
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| Rok vydání: | 2011 |
| Předmět: |
Caulobacter
Anti-HIV Agents HIV Infections HIV Antibodies Antiviral Agents Epitope Neutralization Microbiology law.invention Drug Delivery Systems Neutralization Tests law Caulobacter crescentus Humans Pharmacology (medical) Pharmacology Membrane Glycoproteins biology biology.organism_classification Virology Recombinant Proteins Infectious Diseases CD4 Antigens HIV-1 biology.protein Recombinant DNA Female Protein G Antibody Genetic Engineering S-layer |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 55:5547-5552 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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