Washington D.C., USA, 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, 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, July 2012www.aids2012.org DNA Immunization Results: MPER-PDGFR-TM Targets Abs against the MPER; MPER-HIV-TM Targets the Cytoplasmic Domain