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Principal Investigator: Erica Ollmann Saphire
Organization: LA JOLLA INSTITUTE FOR IMMUNOLOGY
Fiscal Year: 2024
Award: $274,500
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Vaccines are the greatest bang for our public health buck, yet vaccine development is still sometimes hit or miss.
Recent efforts with SARS-CoV-2 demonstrated that acceleration of vaccine programs is possible, especially
when supported by prior studies characterizing successful immune responses against related prototype
pathogens. The measles virus vaccination campaign is a global success story; the live-attenuated vaccine
developed in the 1960’s still elicits highly protective antibodies to strains circulating today. Yet Measles outbreaks
persist due to obstacles in vaccination programs such as global health inequities, vaccine hesitancy, extreme
weather events related to climate change, and the SARS-CoV-2 pandemic. Furthermore, a growing population
with compromised immune systems cannot receive live-attenuated viral vaccines. Thus, the threat of measles
remains (there are still approximately 9-10 million cases annually), and innovative solutions will be needed to
achieve global measles eradication. However, very little is known about the human antibody response to measles
infection or vaccination beyond neutralizing antibody titers. Importantly, there are no structures of any antibodies
in complex with any measles virus antigens. As a result, we do not know which sites on measles virus are
immunodominant and protective. Much of this fundamental knowledge is lacking largely because measles was
effectively eradicated from developed nations before needed scientific tools had been developed. In this work,
we will use state-of-the-art tools to directly visualize the structure of human antibodies from vaccinee polyclonal
sera bound to measles surface glycoproteins to understand which antigenic sites dominate in the human
vaccinee response. We will also use microfluidics and rapid microscale multiplexed competition analyses to
rapidly discover and analyze individual human monoclonal antibodies against measles virus for the first time.
This work will reveal what components of the human immune response to this prototype paramyxovirus lead to
vaccine-mediated protection, and will help guide development of modern vaccines for the immunocompromised
and other vaccines against paramyxoviruses yet to emerge.
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Microscope><Electron Microscopy><Epitope Mapping><Epitopes><Event><Family><Funding><Genetic Alteration><Genetic Change><Genetic defect><Genetics-Mutagenesis><Glycoproteins><Health Inequity><Hemagglutinin><Hu-mABs><Human><Immune response><Immune system><Immunization><Immunization Programs><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunodominant Antigenic Determinants><Immunodominant Determinants><Immunodominant Domains><Immunodominant Epitopes><Immunodominant Regions><Immunodominant Sites><Immunologic Surface Markers><Immunological Surface Markers><Immunological response><Immunosuppressed Host><Individual><Industrialized Countries><Industrialized Nations><Inequalities in Health><Inequities in Health><Infection><Interruption><Kinetics><Knowledge><Lassa fever virus><Lassa virus><Lead><Learning><Live-attenuated Vaccine><Maps><Measles><Measles virus><Mediating><Membrane Glycoproteins><Mice><Mice Mammals><Microfluidics><Modern Man><Modernization><Molecular Interaction><Monoclonal Antibodies><Murine><Mus><Mutagenesis><Mutagenesis Molecular Biology><Mutation><NIAID><National Institute of Allergy and Infectious Disease><Nature><Negative Staining><Outbreaks><Paramyxoviridae><Paramyxovirus><Pb element><Peptides><Population><Public Health><RNA Viruses><RNA vaccine><RNA-based vaccine><Rapid screening><Reactive Site><Rubeola><SARS><SARS corona virus 2><SARS coronavirus disease><SARS-CO-V2><SARS-COVID-2><SARS-CoV disease><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Serology><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress 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