DNA Vaccines Elicit Antibodies Targeting the MPER of HIV-1 gp41

Washington D.C., USA, 22-27 July 2012www.aids2012.org

DNA Vaccines Elicit Antibodies Targeting the MPER of HIV-1 gp41

Jamie K. Scott, Simon Fraser University, Canada

Funding: NIAID/NIH and CIHR

The MPER of HIV gp41 is discreet 22-AA long region preceding the transmembrane region (TM) of Env.

It is the target of 3 broadly neutralizing antibodies (Abs), and 3 heterologous cross-neutralizing Abs against HIV.

Hypothesis: The MPER’s neutralizing structure depends upon the viral membrane and constraint by the gp41 TM.

Goal: Produce a DNA-prime, protein-boost vaccines that elicit broadly neutralizing Abs against the MPER, by associating it with lipid bilayer and tethering it with a TM.

Washington D.C., USA, 22-27 July 2012www.aids2012.org

DNA Vaccines: The Nature of the TM Affects MPER-binding by Broadly Neutralizing Abs, 2F5 and 4E10

2F5 binds the C-terminus of the MPER, and 4E10 the N-terminus.MPER binding by 2F5 is weakly affected by the TM, whereas MPER binding by 4E10 is stronger in the presence of the HIV TM.

Washington D.C., USA, 22-27 July 2012www.aids2012.org

DNA Immunization Results:MPER-PDGFR-TM Targets Abs against the MPER;

MPER-HIV-TM Targets the Cytoplasmic Domain