1. 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.

2. 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.

3. 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