Research Topics
Humoral immunity is an essential component to clear infections and robust, long-lasting B cell-mediated memory is a correlate of protection for many vaccines. However, numerous factors related to both host and pathogen can influence the quality of humoral memory upon infection and vaccination. Studying the origin, maturation and evolutionary barriers of functionally active B cell clones provides valuable information on the natural history of effective and abherrant B cell reponses and a platform for the rational selection of immunogen designs.
The mission of the Translational Immunobiology Unit is to extend the basic understanding of B cell selection, clonal expansion and maturation into memory responses; to gather information from the natural evolution of B cell responses to inform effective immunogen designs, and to identify prophylactic and therapeutic antibody-based countermeasures. Studies will encompass primarily human and non-human primate specimens, as well as murine models, and will use multiple virus models, including HIV, flaviviruses, influenza virus, herpesviruses and betacoronaviruses.
Biography
Dr. Bonsignori received his M.D. and M.S. in clinical microbiology and virology from the University of Insubria Medical School in Varese, Italy. He conducted postdoctoral research in the Department of Immunology at St. Jude Children’s Research Hospital in Memphis, Tennessee before being appointed research associate at the Duke Human Vaccine Institute, Duke University School of Medicine in Durham, North Carolia, where his activity focused primarily on HIV vaccine development. In 2009, he established the Laboratory of B-cell Repertoire Analysis and ultimately attained the position of associate professor of medicine. In the HIV field, Dr. Bonsignori isolated multiple broadly neutralizing antibody B cell lineages from chronically HIV-1 infected individuals and characterized antibody/virus co-evolution to rationally select immunogen candidates for sequential vaccination schemes. Dr. Bonsignori developed a high-throughput memory B cell culture system for the functional screening of memory B cells at the single-cell level and conceptualized a novel framework for steering the immune response through immunogen design based on the probability of individual mutations and their effect on antibody effector functions. He later applied some of the technologies and workflows to study B cell responses to P. falciparum and Zika virus. Before NIAID, Dr. Bonsignori supported the Duke University student COVID-19 surveillance program by establishing a high-throughput workflow for the rapid accessioning, pooling and storage of nasal swab samples that sustained the screening of up to 20,000 samples per week. Dr. Bonsignori joined the Laboratory of Infectious Diseases in March 2021.
Selected Publications
- Singh T, Hwang KK, Miller AS, Jones RL, Lopez CA, Dulson SJ, Giuberti C, Gladden MA, Miller I, Webster HS, Eudailey JA, Luo K, Von Holle T, Edwards RJ, Valencia S, Burgomaster KE, Zhang S, Mangold JF, Tu JJ, Dennis M, Alam SM, Premkumar L, Dietze R, Pierson TC, Ooi EE, Lazear HM, Kuhn RJ, Permar SR, Bonsignori M. A Zika virus-specific IgM elicited in pregnancy exhibits ultrapotent neutralization. Cell. 2022;185(25):4826-4840.e17.
- Casiano Matos J, Harichandran K, Tang J, Sviridov DO, Sidoti Migliore G, Suzuki M, Olano LR, Hobbs A, Kumar A, Paskel MU, Bonsignori M, Dearborn AD, Remaley AT, Marcotrigiano J. Hepatitis C virus E1 recruits high-density lipoprotein to support infectivity and evade antibody recognition. J Virol. 2024;98(1):e0084923.
- Wiehe K, Saunders KO, Stalls V, Cain DW, Venkatayogi S, Martin Beem JS, Berry M, Evangelous T, Henderson R, Hora B, Xia SM, Jiang C, Newman A, Bowman C, Lu X, Bryan ME, Bal J, Sanzone A, Chen H, Eaton A, Tomai MA, Fox CB, Tam YK, Barbosa C, Bonsignori M, Muramatsu H, Alam SM, Montefiori DC, Williams WB, Pardi N, Tian M, Weissman D, Alt FW, Acharya P, Haynes BF. Mutation-guided vaccine design: A process for developing boosting immunogens for HIV broadly neutralizing antibody induction. Cell Host Microbe. 2024;32(5):693-709.e7.
- Mu Z, Wiehe K, Saunders KO, Henderson R, Cain DW, Parks R, Martik D, Mansouri K, Edwards RJ, Newman A, Lu X, Xia SM, Eaton A, Bonsignori M, Montefiori D, Han Q, Venkatayogi S, Evangelous T, Wang Y, Rountree W, Korber B, Wagh K, Tam Y, Barbosa C, Alam SM, Williams WB, Tian M, Alt FW, Pardi N, Weissman D, Haynes BF. mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice. Cell Rep. 2022;38(11):110514.
- Bonsignori M, Marcotrigiano J. HCV neutralization goes elite. Immunity. 2022;55(2):195-197.
Related Scientific Focus Areas
Microbiology and Infectious Diseases
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This page was last updated on Monday, August 19, 2024