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Grant: CIHR Fellowship

Direct Payment

$150,000.00

Using LIBRA-seq to identify broadly-reactive influenza antibodies in human respiratory tissues for translation into novel monoclonal therapeutics

FY 2022-23

Summary
Despite being identified 90 years ago, influenza virus remains one of the most dangerous respiratory pathogens worldwide. Each year, circulating influenza strains mutate to evade pre-existing immunity and kill ~400 000 people. In addition, unique strains occasionally jump from animals (pigs, birds) to cause "flu" pandemics, which can take substantially more lives. Currently, vaccines for influenza are strain-specific (they target viral regions that often mutate between strains) and provide unpredictable and variable protection. In addition, influenza can easily develop resistance against existing antiviral drugs. Thus, despite significant research, humans remain under the constant burden of seasonal infections, threat of pandemics, and are poorly prepared to treat influenza infections once they begin. My research program in the laboratory of Dr. Patrick Wilson at Weill Cornell Medicine aims to address part of this preparedness gap by searching for rare molecules which can directly protect from, and inform vaccine design against, many different influenza strains: broadly-protective antibodies. My work will use cutting edge technology ("LIBRA-seq") to isolate and assess "memory B cells" from organ-donor lungs, and surgically-removed tonsils from children and adults. In particular, we will study cells specific for parts of influenza which do not easily mutate. We will then use the unique genetic information from these cells to produce their antibodies in the laboratory. Having enriched antibodies which appear to be "broadly-reactive", we will test each for its true ability to provide protection against a wide array of influenza strains. Using this approach, we aim to identify broadly-protective antibodies which can be developed as clinical treatments against influenza, and can provide information critical to designing next-generation "universal" influenza vaccines, all while improving our understanding of how children and adults respond differently to infection.
Program
CIHR Fellowship
Location
New York, United States of America
Type
Grant
Source
CIHR Funding Decisions Database

As published

Id
473524
Name
McGrath Joshua J
Region
New York
Country
United States of America
Orgtype
Research Institution
Instname2
Infection and Immunity
Theme2
Biomedical
Prcname2
Fellowships - Post-PhD
Projecttitle
Using LIBRA-seq to identify broadly-reactive influenza antibodies in human respiratory tissues for translation into novel monoclonal therapeutics
Programtype2
Fellowship Programs
Orgnameinp2
Direct Payment
Cihramount2
$150,000
Cihrequipment2
$0
Programname2
CIHR Fellowship
Keyworddelim
Broadly-Protective Antibodies; Children; Influenza; Lungs; Mediastinal Lymph Nodes; Memory B Cells; Tonsils; Translational
Abstract
Despite being identified 90 years ago, influenza virus remains one of the most dangerous respiratory pathogens worldwide. Each year, circulating influenza strains mutate to evade pre-existing immunity and kill ~400 000 people. In addition, unique strains occasionally jump from animals (pigs, birds) to cause "flu" pandemics, which can take substantially more lives. Currently, vaccines for influenza are strain-specific (they target viral regions that often mutate between strains) and provide unpredictable and variable protection. In addition, influenza can easily develop resistance against existing antiviral drugs. Thus, despite significant research, humans remain under the constant burden of seasonal infections, threat of pandemics, and are poorly prepared to treat influenza infections once they begin. My research program in the laboratory of Dr. Patrick Wilson at Weill Cornell Medicine aims to address part of this preparedness gap by searching for rare molecules which can directly protect from, and inform vaccine design against, many different influenza strains: broadly-protective antibodies. My work will use cutting edge technology ("LIBRA-seq") to isolate and assess "memory B cells" from organ-donor lungs, and surgically-removed tonsils from children and adults. In particular, we will study cells specific for parts of influenza which do not easily mutate. We will then use the unique genetic information from these cells to produce their antibodies in the laboratory. Having enriched antibodies which appear to be "broadly-reactive", we will test each for its true ability to provide protection against a wide array of influenza strains. Using this approach, we aim to identify broadly-protective antibodies which can be developed as clinical treatments against influenza, and can provide information critical to designing next-generation "universal" influenza vaccines, all while improving our understanding of how children and adults respond differently to infection.
Competitiondate
202210
Approvedterm2
3 yrs 0 mth
Pinamesdelim
McGrath, Joshua J
Approvedterm
3 ans 0 mois
Cihrcontribution2
~ $150,000~ $0~
Direct Payment - $150,000 Grant (2022-23) | Canada Spends