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Principal Investigator: Mattia Bonsignori
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $1,670,518
Funding agency: National Institute of Allergy and Infectious Diseases
The human immune system generates a diverse repertoire of pathogen-binding proteins called antibodies secreted by terminally differentiated short- and long-lived plasma cells as well as antigen-experienced B cells which constitute a pool of memory B cells that can further mature upon re-engagement in recall responses. Virus neutralizing antibodies are the correlate of protection for many licensed vaccines. While diversity in the antibody repertoire is essential to effective antiviral responses, the engagement of pre-existing B cells stimulated by a prior infection can lead to the expansion of suboptimal responses both in the settings of natural infection and upon vaccination. This phenomenon is known as antigenic sin. Antigenic sin has been documented for influenza and it has been evoked as the underlying cause of antibody-dependent enhancement of infectivity in sequential flavivirus infections (e.g., Zika and Dengue viruses).
Antigenic sin can also play a role in the context of sequential immunization regimens or repeated vaccinations. Despite extensive investigations and considerable progress, highly mutating viruses still present considerable challenges to the development of effective (e.g., HCV and HIV-1) or durable vaccines (e.g., influenza virus, SARS-CoV-2), as they can quickly escape control from neutralizing antibodies. In these cases, vaccine formulations that comprise multiple immunogens, administered either concomitantly or sequentially, are likely needed to elicit adequately affinity matured broadly neutralizing antibodies. In the context of vaccination, the format in which immunogens are presented may also influence the balance between recall and de novo responses.
Therefore, furthering our understanding of the ontogeny and maturation of memory B cell responses in the contexts of natural infection and vaccination and the role of cross-reactivity in shaping the memory B cell response are essential to inform successful immunogen design strategies and better understand the natural development of humoral immunity. The activity of the TIU is centered on studying the ontogeny and maturation of protective memory B cell responses in multiple virus models to identify novel and generalizable criteria pertaining B cell maturation. A special area of interest of the TIU pertains the origins, role and plasticity of IgM-positive memory B cells in protection from viral infections, including flaviviruses, for which persistent IgM responses have been documented.
Terms: <19S Gamma Globulin><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Affinity><Anti-viral Response><Antibodies><Antibody Repertoire><Antibody Therapy><Antibody-Dependent Enhancement><Antigens><Area><Avian Influenza A Virus><Avian Influenza Virus><Avian Orthomyxovirus Type A><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding Proteins><Blood Plasma Cell><Breakbone Fever Virus><COVID-19 virus><COVID19 virus><Cell Maturation><Clonal Expansion><CoV-2><CoV2><DENV><Dengue Virus><Dengue fever virus><Development><Equilibrium><Evolution><Flavivirus><Flavivirus Infections><Fowl Plague Virus><Generalized Growth><Grippe><Group B Arbovirus><Growth><HCV><HIV-1><HIV-I><HIV1><Hepatitis C virus><Human><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Humoral Immunities><IgM><Immune system><Immunity><Immunization><Immunobiology><Immunoglobulin M><Immunophysiology><Infection><Influenza><Influenza Virus><Investigation><Licensing><Ligand Binding Protein><Ligand Binding Protein Gene><Memory><Memory B Cell><Memory B-Lymphocyte><Modeling><Modern Man><Mutate><Myxovirus pestis galli><Orthoflavivirus><Plasma Cells><Plasmacytes><Preventative vaccine><Preventive vaccine><Prophylactic vaccine><Protein Binding><Regimen><Research><Research Specimen><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Shapes><Specimen><Tissue Growth><Vaccination><Vaccines><Viral Diseases><Virus><Virus Diseases><Wuhan coronavirus><ZIKV><Zika Virus><antibody based therapies><antibody treatment><antibody-based immunity><antibody-based therapeutics><antibody-based treatment><avian flu virus><balance><balance function><bird flu virus><bound protein><coronavirus disease 2019 virus><coronavirus disease-19 virus><cross reactivity><design><designing><developmental><experience><hCoV19><immunogen><influenzavirus><information gathering><innovate><innovation><innovative><interest><nCoV2><neutralizing antibody><non-human primate><nonhuman primate><novel><ontogeny><pathogen><pathogenic virus><plasmocyte><prophylactic><response><social role><translational goal><translational mission><vaccine formulation><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease><zikav>