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Principal Investigator: Duane R. Wesemann
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2022
Award: $686,383
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Antibodies specific for pathogenic threats can provide immediate protection from infectious disease but
longevity of an antibody responses after vaccination or infection can be highly variable. Responses induced by
some live vaccines can persist for a lifetime, whereas protein-based vaccines are in general shorter lasting.
However, antibody durability is not necessarily linked to the use of live virus as long-lived antibody responses
have been shown to be induced by the human papilloma virus (HPV) vaccine, a non-live viral-like particle-
based platform. This suggests that distinct immunological cues can be engineered to result in the generation of
longer-lived antibody responses. While memory lymphocytes also provide a system of protective efficacy,
strategies to maximize robust levels of protective secreted antibodies that are stable over time is an important
goal in modern immunology. Understanding the capabilities of the immune system in this context, and how
available vaccines can elicit durable secreted antibody responses will be important to decipher. This is relevant
to the ongoing SARS-CoV-2 pandemic and for vaccine strategies more broadly. Preliminary data suggest that
antibodies induced by natural infection harbor robust long-term stability at modest levels and greater polyclonal
neutralizing breadth across viral variants compared to infection-naïve vaccinees. In addition, differential
antibody durability trajectories tend to favor COVID-19 convalescent subjects with dual memory B cell features
of greater antibody somatic mutation and cross-coronavirus reactivity. These findings support a hypothesis that
high somatical mutation and cross-reactivity in antigen-binding memory B cell repertoires early after recovery
predicts antibody durability and that recalled immunity may confer greater longevity of differentiated plasma
cells. This hypothesis will be examined in two aims, (i) to illuminate factors influencing anti-SARS-CoV-2
antibody durability, and (ii) to chart the functional evolution of anti-CoV memory B cell over time. For aim 1,
human and mouse studies will be used to illuminate potential mechanistic insights and features connected to
durable antibody responses. For aim 2, the durability and evolution of memory B cell repertoire antigen
recognition capacity will be charted over time to assess the evolving relationship between secreted polyclonal
and memory B cell repertoires. This work is expected to shed light on factors that influence longevity and
evolution of antibody responses, which will be important for ongoing improvement of vaccine strategies.
Terms: <7S Gamma Globulin><Affinity><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antibody-Secreting Cells><Antigenic Determinants><Antigens><Attenuated Vaccines><Automobile Driving><B blood cells><B cell><B cell repertoire><B cells><B-Cell Activation><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><Blood Plasma Cell><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 antibody><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 public health crisis><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 infection><COVID19 pandemic><COVID19 public health crisis><CV-19><CV19><Cell Communication><Cell Interaction><Cell-to-Cell Interaction><Clone Cells><Communicable Diseases><Coronaviridae><Coronavirus><Cues><Data><Disease><Disorder><Dose><Engineering><Epitopes><Evolution><Frequencies><Future><Generations><Genetic Alteration><Genetic Change><Genetic defect><Germinal Center><Goals><HPV Vaccine><Human><Human Papilloma Virus Vaccine><Human papillomavirus Vaccine><Ig Somatic Hypermutation><IgG><Immune><Immune Globulins><Immune response><Immune system><Immunes><Immunity><Immunochemical Immunologic><Immunoglobulin G><Immunoglobulin Somatic Hypermutation><Immunoglobulin-Secreting Cells><Immunoglobulins><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Length of Life><Light><Link><Live-attenuated Vaccine><Longevity><Lymphatic cell><Lymphocyte><Lymphocytic><Memory><Memory B Cell><Memory B-Lymphocyte><Mice><Mice Mammals><Modern Man><Modernization><Molecular Interaction><Murine><Mus><Mutation><Pathogenicity><Photoradiation><Plasma Cells><Plasmacytes><Proteins><Public Health><RNA immunization><RNA vaccination><Recovery><Research><SARS-CoV-2 antibody><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV2 antibody><SARS-CoV2 epidemic><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Sampling><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Somatic Mutation><Speed><Structure of germinal center of lymph node><System><T-Cells><T-Lymphocyte><Testing><Time><Vaccination><Vaccine Design><Vaccinee><Vaccines><Variant><Variation><Viral><Virus><Work><access to vaccination><access to vaccines><activated B cells><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after severe acute respiratory distress syndrome CoV-2 infection><allergic/immunologic body system><allergic/immunologic organ system><antibody against COVID-19><antibody against SARS-CoV-2><antibody against SARS-CoV2><antibody against coronavirus disease 2019><antibody against severe acute respiratory syndrome coronavirus 2><antibody to COVID-19><antibody to SARS-CoV-2><antibody to SARS-CoV2><antibody to coronavirus disease 2019><antibody to severe acute respiratory syndrome coronavirus 2><antigen binding><antigen bound><base><cohort><corona virus><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 antibody><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><cross reactivity><driving><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following severe acute respiratory distress syndrome CoV-2 infection><genome mutation><host response><immune system response><immunogen><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><insight><life span><lifespan><live vaccine><live vaccines><lymph cell><mRNA immunization><mRNA vaccination><model of animal><model organism><neutralizing antibody><particle><pathogen><plasma cell differentiation><plasmocyte><polyclonal antibody><post SARS-CoV-2 infection><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><prophylactic><protective efficacy><response><severe acute respiratory syndrome coronavirus 2 antibody><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><somatic hypermutation><thymus derived lymphocyte><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination access><vaccination availability><vaccine access><vaccine availability><vaccine strategy>