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Analysis of SIVmac Envelope-Specific Antibodies Selected Through Phage Display
Sergio Ita1,2, Mayara R Agostinho1,3, Katherine Sullivan1
11 Biology Department, Boston College , Chestnut Hill, Massachusetts.
AIDS Research and Human Retroviruses
|January 12, 2017
Summary
Researchers developed a phage display library from SIV-infected macaques to identify antibodies against SIV envelope glycoproteins. While most antibodies didn't neutralize resistant SIV strains, many effectively neutralized a different SIV strain.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Rhesus macaques infected with simian immunodeficiency virus (SIV) can develop high-titer neutralizing antibodies.
- Understanding antibody responses is crucial for developing effective vaccines and therapies against SIV and HIV.
Purpose of the Study:
- To construct and screen a single chain fragment variable (scFv) phage display library from an SIV-infected rhesus macaque.
- To identify and characterize SIV envelope (Env)-specific monoclonal antibodies (mAbs) and analyze their variable gene usage and neutralization capabilities.
Main Methods:
- Construction of an scFv phage display library from an SIV-infected rhesus macaque.
- Screening the library using SIVmac239 trimeric (gp140) and monomeric (gp120) envelope glycoproteins.
- Cloning variable-heavy and variable-light (VH-VL) antibody fragments from B-cell lines producing SIV gp120-specific mAbs.
- Assessing antibody neutralization activity against tier-1 and tier-3 SIV strains.
Main Results:
- Thirty-two gp140-specific and 20 gp120-specific mAbs were selected.
- gp120-specific mAbs were exclusively from the VH4 family; gp41-specific mAbs were primarily from VH1, VH4, and VH3.
- A preferential VH-VL combination was observed in phage display-selected SIV Env-specific mAbs.
- None of the tested antibodies neutralized tier-3 SIVmac239, but most gp120-specific mAbs potently neutralized tier-1 SIVmac316.
Conclusions:
- The study identified SIV Env-specific antibodies from rhesus macaques with distinct variable gene segment usage.
- These antibodies, particularly gp120-specific ones, show potent neutralization of tier-1 SIV strains.
- The findings provide insights into antibody responses in SIV infection and useful reagents for further research.
