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Principal Investigator: Galit Alter
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2022
Award: $26,206
Funding agency: National Institute of Allergy and Infectious Diseases
Since 2002, several coronaviruses have emerged able to cause severe respiratory disease, however no vaccine is available to prevent these rapidly spreading pathogens. Vaccine design has specifically lagged due to our lack of understanding of the correlates of immunity against these pathogens. Both cellular and humoral immune responses have been implicated in resolution of disease, but to date only the passive transfer of antibodies has been shown to confer complete protection in mice. Interestingly, the transfer of both “neutralizing” and nonneutralizing antibodies have shown protective efficacy, highlighting the role of multiple humoral mechanisms in limiting viral infection/spread. The precise mechanism of action of these antibodies that have the most profound impact on limiting disease is currently unclear, but if elucidated could provide critical insights for the development of effective vaccines against COVID-19 and other coronaviruses. Thus, here we aim to take a systematic approach to dissect and define both the polyclonal and monoclonal mechanisms by which antibodies confer protection against COVID-19. Specifically, samples from DNA- and adenovirus 26 (Ad26)- COVID-19 Spike protein (S) immunized animals, that will be challenged with COVID-19, will be comprehensively profiled using Systems Serology, to define the functional humoral immune responses linked to protection from infection/disease in mice, ferrets, and macaques. Machine learning modeling will be employed to discern key immune response features that translate usefully across these diverse animal contexts. These studies will not only define correlates of immunity across vaccines and species, but also provide mechanistic insights into the precise mechanisms by which antibodies may confer protection in the context of future vaccines.
Terms: <2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><Adenoviridae><Adenoviruses><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antibody Response><COVID-19><COVID-19 S protein><COVID-19 immunity><COVID-19 infection><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID19><COVID19 S protein><COVID19 immunity><COVID19 infection><COVID19 spike glycoprotein><COVID19 spike protein><CV-19><CV19><Coronaviridae><Coronavirus><DNA><Deoxyribonucleic Acid><Development><Disease><Disorder><Ferrets><Future><Immune><Immune response><Immunes><Immunity><Immunize><Immunological response><Immunomodulation><Infection><Lead><Link><M mulatta><M. mulatta><Macaca><Macaca mulatta><Macaque><Mice><Mice Mammals><Murine><Mus><Passive Antibody Transfers><Passive Transfer of Immunity><Pb element><Resolution><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Rhesus Macaque><Rhesus Monkey><Role><SARS-CoV-2 S protein><SARS-CoV-2 immunity><SARS-CoV-2 infection><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2 S protein><SARS-CoV2 infection><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><Sampling><Serology><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 immunity><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><System><Translating><Vaccination><Vaccine Design><Vaccines><Viral Diseases><Virus Diseases><Work><corona virus><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 S protein><coronavirus disease 2019 immunity><coronavirus disease 2019 infection><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease-19><coronavirus infectious disease-19><develop a vaccine><develop vaccines><development of a vaccine><developmental><heavy metal Pb><heavy metal lead><host response><immune modulation><immune regulation><immune system response><immunity against COVID-19><immunity against COVID19><immunity against SARS-CoV-2><immunity against Severe acute respiratory syndrome coronavirus 2><immunity against coronavirus disease 2019><immunity to COVID-19><immunity to COVID19><immunity to SARS-CoV-2><immunity to Severe acute respiratory syndrome coronavirus 2><immunity to coronavirus disease 2019><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><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><machine learning based model><machine learning model><model of animal><model organism><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><novel drug treatments><novel drugs><novel therapeutics><novel therapy><pathogen><prevent><preventing><protective efficacy><social role><vaccine development><viral infection><virus infection><virus-induced disease>