INVESTIGATORS & CORES
This project brings together collaborating groups at Boston Children's Hospital and Harvard Medical School (Harrison), the Duke Human Vaccine Institute (DHVI)(Moody, Sempowski), the Duke University School of Medicine Department of Immunology (Kelsoe, Kuraoka), the Ragon Institute of MGH, MIT and Harvard (Schmidt), and Dartmouth College (Lee). It capitalizes on the powerful technologies they together command, to probe B-cell dynamics and antibody output in the response to influenza vaccination and infection.
PI of the P01 and PI of Project 4 (Structural biology of influenza Ab-antigen interactions) and Core A (Administration)
Giovanni Armenise-Harvard Professor of Basic Biomedical Sciences at Harvard Medical School and Boston Children's Hospital and Investigator in the Howard Hughes Medical Institute. He is Head of the Laboratory of Molecular Medicine at Children's Hospital and Faculty Director of the Harvard cryo-EM Center for Structural Biology. He is a leading expert on the structure of viruses and viral proteins, as studied at high resolution by x-ray crystallography and by cryo-EM. He has worked on the surface glycoproteins of flaviviruses, herpesviruses, coronaviruses, and HIV/SIV and on the fusion mechanisms of viral fusion proteins, as well as on influenza virus immunology, as head of this project for the past ten years.
M. ANTHONY MOODY
PI of Project 1 (Human and non-human primate B-cell and serum Ab repertoire)
Professor of Pediatrics and Immunology at Duke and an experienced clinician in Pediatric Infectious Diseases. He also serves as the principal investigator of the Duke CIVIC Vaccine Center (DCVC) at the Duke Human Vaccine Institute. The DCVC is one of three vaccine discovery centers in the NIH-funded Collaborative Influenza Vaccine Innovation Centers program, working to develop the next generation of influenza vaccines. Dr. Moody joined the faculty at Duke in 2006, after receiving his MD from Duke University School of Medicine in 1999 and training in Pediatrics (Emory) and Pediatric Infectious Diseases (Duke). His primary basic research interest is the B cell response to vaccination, infection, and autoimmune disease. His current research is on influenza, syphilis, and HIV.
PI of Core B (Virology)
Professor in the Departments of Medicine and Pathology at Duke School of Medicine and primary faculty in the Duke Human Vaccine Institute (DHVI). He is Director of the Duke RBL and Scientific Director for all DHVI Core Facilities, with over 20 years of research experience, including vaccine and therapeutics development for emerging infectious diseases. He is the lead of the Duke CIVICS Vaccine Center Immunological Analyses Unit, providing full pre-clinical cellular, humoral and molecular characterization of immune responses (human, mouse, ferret, NHP) to develop seasonal and universal influenza vaccines. He is lab oversight and harmonization lead for the Coordinating Center in the newly created Centers for Research in Emerging Infectious Diseases Network (CREID; NIAID-DMID).
PI of Project 2 (Affinity maturation of the B-cell repertoire)
Vaccine Institute. He is an expert in the biology and somatic genetics of B lymphocytes and pioneered our current understanding of B-cell hypermutation and affinity-driven selection in germinal centers. He has long standing collaborations with B.F. Haynes to study the role of immunological tolerance in the prevention of robust humoral immunity to HIV-1. Work with T. Nojima, A.G. Schmidt, and S.C. Harrison have focused on the population genetics of humoral responses to influenza HA. The novel cloning methods developed in Kelsoe’s laboratory will be used to illuminate the phenomenon of clonal imprinting characteristic of serial influenza exposures.
co-Investigator, Project 2, and PI of Core D (Bmem analysis)
Assistant Research Professor in the Department of Immunology at Duke University. He has made important contributions to our understanding of central B-cell tolerance and the B-cell selection in response to immunizations and infections. With colleagues, he established the Nojima culture method for mouse B cells and adapted it to human B cells, the fundamental technology of Core D. He has 20 years of basic science experience in B lymphocyte biology and mucosal immunity in mice and humans. He will provide the day-to-day supervision, direction and oversight for all core personnel; he will be responsible for the analysis and interpretation of the data and their transfer to P01 investigators.
AARON G. SCHMIDT
PI of Project 3 (Influenza virus HA and NA immunogen design)
Assistant Professor of Microbiology in the Department of Microbiology at Harvard Medical School and of Immunology at Massachusetts General Hospital, and Group Leader at the Ragon Institute of MGH, MIT and Harvard. His postdoctoral work led to key papers for this Program Project characterizing structurally and biochemically the humoral response to influenza HA, particularly the RBS. As Project 3 lead, he will continue to use structure-guided protein engineering and contemporary methods for protein directed evolution to design immunogens focused on conserved viral sites and to develop novel immunogens for asking basic questions about the humoral immune response. His expertise in these areas, complementary to those of the other Project leads, will contribute critically to completing our overall goals.
PI of Core C (IgSeq and NGS)
Ralph and Marjorie Crump Assistant Professor of Engineering at Dartmouth College. He is an expert in immune profiling of Ab repertoire in humans using cutting-edge technologies involving high-throughput sequencing of B cells (BCR-Seq) and proteomic deconvolution of serum Abs (Ig-Seq). His research program focuses on understanding how the infectious pathogen-specific Ab repertoire in circulation and mucosal sites develop and subsequently bias humoral immune responses to repeated exposures, particularly focused in the context of influenza and other infectious diseases. He has collaborated with the investigators of the Program Project since 2014.
Two international leaders in vaccine immunology serve as consultants to the PO1:
BARTON F. HAYNES
Frederic M. Hanes Professor of Medicine and Immunology and Director of the Human Vaccine Institute at Duke, as well as Principal Investigator for the Center for HIV/AIDS Immunology -- Immunogen Design (CHAVI-ID) and PI of a Gates Collaboration for AIDS Vaccine Discovery (CAVD) Center grant. In these roles, Dr. Haynes has led the development of much of the technology for analysis of naïve B-cell repertoires in acute HIV infection -- efforts that have in turn led to the strategies adopted in Project 1. The Program Project and its PI will continue to benefit greatly from Dr. Haynes expertise in B-cell immunology, from his long experience in vaccine research, and from his outstanding track record in organizing and leading large, interdisciplinary research teams.
Dula D. Cockrell Centennial Chair in Engineering #2 at University of Texas, Austin. Dr. Georgiou's laboratory has developed the elegant mass-spectrometry methods that enable deconvolution of amino-acid sequences in serum Abs (Ig-seq) and the high-throughput, single-cell, paired-chain NGS method that Dr. Lee has implemented in Core C. He has been a collaborator with the Program Project in the previous cycle and in the first two years of the current cycle. He has transferred that responsibility to his former student, Dr. Jiwon Lee, who will lead Core C. His deep understanting of immune repertoires and their analysis will be of great value to the project team.
External Scientific Advisory Board:
Sir John J. Skehel, Francis Crick Institute, London, UK
Prof. Eric Meffre, Yale University, New Haven, CT
Dr. Philip R. Dormitzer, Pfizer Vaccines, Pearl River, NY