Annual and Interim Progress Report Summaries
Principal Investigator: Robin Weiss
Project: Vaccine-Induced Protective Cross-Neutralization of HIV-1
Submitted January 14, 2010
Research objectives for our consortium:
1. Identify novel monoclonal antibodies that cross-neutralize HIV-1 between and within Clades.
2. Direct the selection of novel immunogens recognized by these monoclonal antibodies. These novel immunogens will serve as the basis for the creation of HIV-1 vaccine candidates.
3. Demonstrate the ability of these novel immunogen vaccine candidates to elicit anti-HIV-1 antibodies in animal models. Successful candidates may progress to testing in clinical trials.
Scientific achievements since February 2008:
• Isolated 98 MAbs from memory B cells of HIV-1 infected recruited in Antwerp & London
• Isolated over 50 NMabs from llamas which showed a broad neutralization profile and recognized epitopes in the CD4 binding site, a CD4-induced epitope (CD4i) and gp41 including MPER
• Isolated 69 human IgM monoclonals specific for gp140 from the HuIg mice, including F44, which is of particular interest
• Developed novel Ag screening methods tested with known NMAbs
• Developed novel, improved epitopes and mimotopes on scaffolds which were tested as antigens
• Developed novel VLPs and MAb derived novel Env structures which were tested as antigens
• Characterised 5 different gp41 antigens which were provided for rabbit immunization studies. Structural studies of other NMAbs are ongoing.
• Initiated macaque studies with novel NMAb showing successful post challenge protection.