Program Schedule

1611
Antibodies to conformational epitopes interfere with T20 fusion inhibition

Session: Poster Abstract Session: HIV: Basic Science
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: The Human Immunodeficiency Virus (HIV) is an RNA-enveloped virus that fuses with human CD4+ cells during infection. Fusion occurs when the viral envelope glycoprotein binds with the CD4 cell receptor and two co-receptors on the T-cell. The functional viral envelope glycoprotein spike is a trimeric structure composed of three heterodimers of gp120 and gp41 proteins. When the receptor-binding domain of gp120 interacts with the CD4 receptor, it induces a conformational change in the heterotrimer that fuses the viral envelope membrane to the target cell, thus forming syncitia. Antibodies that form against structural epitopes on the surface of this heterotrimeric envelope spike are hypothesized to be more efficient at blocking this fusion. Other antibodies have been shown to interfere with the fusion inhibitor T20, an analog of the gp41 heptad repeat 2 region. 

Methods: Our lab has previously isolated the antibody gene sequences of a number of trimer-specific antibodies. These bind to four seemingly conformational epitopes. We established an assay to assess functional interference with T20 fusion inhibition. We then screened a panel of control antibodies and trimer-specific and neutralizing antibodies in this assay. 

Results: Two of our trimer specific antibodies that were epitope mapped to gp41 inhibit fusion of t20 in this assay.  We established a production and functional screening method for antibodies that target structural epitopes to HIV and report novel findings that our trimer-specific gp41 targeting Abs interfere with T20 fusion inhibition.

Conclusion: Antibodies targeting these epitopes have implications in both potential therapy strategies and vaccine development.

Hakimuddin Sojar, PhD1, Michele Smith, BA1 and Mark Hicar, MD, PhD2, (1)University at Buffalo, Buffalo, NY, (2)Pediatrics, Microbiology and Immunology, Women and Children's Hospital of Buffalo, University at Buffalo, Buffalo, NY

Disclosures:

H. Sojar, None

M. Smith, None

M. Hicar, None

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