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Assembly and Purification of Prototype Foamy Virus Intasomes
Published on: March 19, 2018
Single-chain Fv-based anti-HIV proteins: potential and limitations
Anthony P West1, Rachel P Galimidi, Priyanthi N P Gnanapragasam
1Division of Biology, California Institute of Technology, Pasadena, California, USA.
Journal of Virology
|October 21, 2011
Summary
Potent antibodies targeting HIV-1 can prevent infection. Researchers compared engineered antibody forms (immunoadhesins) to original antibodies, finding reduced potency but potential for new combination therapies against HIV-1.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- Broadly neutralizing antibodies (bNAbs) against HIV-1 show promise for passive immunization or gene therapy.
- Smaller antibody formats, like immunoadhesins (scFv-Fc), are advantageous for tissue penetration and gene therapy vector capacity.
Purpose of the Study:
- To compare the neutralization potencies of immunoadhesin forms of HIV-1 bNAbs with their parent IgGs.
- To explore the potential of engineered antibody formats for enhanced HIV-1 prophylaxis.
Main Methods:
- Investigated neutralization potencies of immunoadhesins derived from VRC01, PG9, and PG16 antibodies.
- Assessed the impact of dimerization/multimerization on VRC01 immunoadhesin potency.
- Constructed and evaluated a bispecific reagent by linking VRC01 scFv to PG16 IgG.
Main Results:
- Immunoadhesins generally exhibited modestly reduced neutralization potencies compared to parent IgGs, likely due to lower affinities.
- The VRC01 immunoadhesin showed decreased potency when forming dimers and multimers.
- A bispecific reagent combining VRC01 scFv and PG16 IgG demonstrated neutralization activity from both components, with reduced escape by certain HIV-1 strains.
Conclusions:
- While immunoadhesins may have reduced affinity, they offer a platform for creating multifunctional reagents.
- Engineered bispecific antibodies can combine neutralization activities and broaden the spectrum of activity against HIV-1, potentially overcoming viral escape mechanisms.
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