Immune Recognition

Dr. Munir Alam is an Professor of Medicine at Duke University and Director of the Duke Human Vaccine Institute Proteomics Core and Laboratory of Immune Recognition. The Alam laboratory's basic research is targeted at developing new ways to monitor and enhance vaccine responses. As a principal investigator in the Human Vaccine Institute and a member of the Center for HIV/AIDS Vaccine Immunology (CHAVI), the Alam Laboratory’s research work is currently focused on both arms of the host immune system-T and B cell responses.

As a member of CHAVI, Dr. Alam is collaborating with Dr. Haynes and other Human Vaccine Institute Investigators in efforts to understand binding properties and specificity of broadly neutralizing antibodies that bind to the membrane proximal external region (MPER) of HIV-1 Envelope. His group has developed a multiplex surface plasmon resonance (SPR)-based antibody screening assay for binding specificity and avidity measurements in immunized animals and patient samples. They are also using mass spectrometry based proteomic tools to identify neutralizing epitopes on native HIV-1 virions. As part of the Haynes Vaccine Discovery Consortia (VDC) in the Collaboration of AIDS Vaccine Discovery (CAVD), Dr. Alam’s lab is particularly interested in understanding the basis of polyspecificity of broadly neutralizing MPER mAbs and the relevance of antibody membrane lipid binding in HIV-1 neutralization. His group has designed gp41 peptide lipid conjugates using 4E10 and 2F5 epitope peptides and has characterized the binding kinetics, and thermodynamic properties of 4E10 and 2F5 binding to peptide-lipid conjugates. Their recent work with 4E10 and 2F5 CDRH3 mutants suggests that viral membrane lipid binding may be a required initial step for HIV-1 neutralization by MPER neutralizing antibodies. Several of these synthetic liposomes that present MPER peptide epitopes have also been conjugated to Toll like receptor agonists and are being used as immmunogen-adjuvant complexes for the induction of neutralizing antibodies.

The Alam lab also has interest in understanding the trimolecular interactions between membrane bound T cell receptor (TCR-CD3 complex) and its ligand, the peptide-MHC complex (pMHC), and co-receptor molecules. His group has developed a novel biosensor assay for measuring binding kinetics of peptide-MHC monomers and tetramers to T cell receptor expressed on lipid microdomains. This technique has important applications in characterizing antigen specific T cell responses on the basis of TCR avidity. His group is interested in understanding the role of Toll-like receptor (TLR) expression on CD8 T cells and the design of bi-epitope ligands (peptide plus TLR ligand) for the enhancement of T cell responses against low affinity ligands. A potential application of this research in vaccine development will be in developing means to enhance T cell responses against low affinity antigens.

Dr. Alam is also involved in a collaborative project on Computational Immunology with HVI Investigator Dr. Greg Sempowski and led by Dr. Tom Kepler (Multiscale Integrative Immunology for Adjuvant Development), Department of Biostatistics and Bioinformatics, Duke University. They are working to build computational tools for assessment of the role of adjuvants in germinal center B cell development by using SPR based antibody avidity measurements and immunohistology of draining lymph nodes. Dr. Alam is also engaged in inter-disciplinary collaborative research projects with investigators in the Dept. of Mechanical and Bio-Engineering, Duke University. They are utilizing Atomic Force Spectroscopy to measure the unbinding forces of receptor-ligand interactions at the single molecule level. These studies have applications in diagnostics development.

The Alam Lab also serves as the DHVI Biomolecular Interaction Analysis Core (BIA Core), which provides specialized applications and support in SPR, and mass spectrometry- based biomolecular interaction analyses to basic and clinical researchers within the Duke Community. The facility offers state-of-the-art SPR BIAcore instruments for monitoring real time interaction analyses and diverse sets of measurements that include binding affinity, kinetics, epitope mapping and resolution of binding mechanism and structure. The BIA Shared Resource is also integrated with the Mass Spectrometry-Proteomics Shared Resource and offers applications in SPR-MS, in which a bound molecule is eluted and directly spotted on MALDI target plates for a MALDI mass spectrometry based identification of ligands for orphan receptors.