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A Universal Flu Vaccine Based On Conformationally Locked Soluble Headless HA

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 6R44AG059371-04
Agency Tracking Number: R44AG059371
Amount: $1,973,897.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIA
Solicitation Number: PA16-302
Timeline
Solicitation Year: 2016
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-01-10
Award End Date (Contract End Date): 2020-11-30
Small Business Information
140 58TH ST STE 8J, Brooklyn, NY, 11220-2539
DUNS: 081210149
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 MARK YONDOLA
 (631) 235-9297
 yondola@calderbiosciences.com
Business Contact
 CHRISTOPHER MARSHALL
Phone: (917) 806-4057
Email: cmarshall@calderbiosciences.com
Research Institution
N/A
Abstract
An Influenza pandemic remains an acute threat to world healthand stockpiling a universally protective Influenza vaccine provides a strong defense against this potential catastropheThe hemagglutininHAprotein is the primary target of humoral Ab responses to Influenzathe majority of broadly protective mAbsbnAbsagainst influenza isolated from humans recognize conserved and conformation specific epitopes in the HA StalkButstrain specificimmunodominant epitopes in the Head of HA overwhelm immune responses to the StalkAn HA immunogen from which the Head domain has been removed will elicit anti Stalk antibodies that protect broadly against seasonalas well as pandemicInfluenzaDespite significant progressit has so far not proved possible to design a stable Headless HA that assumes its fully native conformation and thereby elicits universally protective Ab responsesNone of the most promisingrecent designs have progressed to clinical developmentAvatar has developed a strategy to produce a conformationally intact Headless HA that overcomes these limitationsThis strategy involves first locking the structure of the conserved Stalk with target dityrosineDTcrosslinksso that it can no longer lose its native conformationThen we remove the variable and immunodominant Head domain with a site specific proteaseusing engineered recognition sitesThis DTHeadless HA immunogen is in its fully native conformationand responses to this more perfect immunogen will improve Ab titers and affinities to conserved epitopesand thus protect broadly against all strains of InfluenzaIn Phase Iwe successfully designed and characterized our DT Headless HAAIIn Phase II we will demonstrate heterologous protection in Balb c mouse challenge studiesand confirm efficacy of this product in ferret challenge studiesAimsandampWe will also transfer our design into a Group II HA and test its heterologous protection in mouse and ferret lethal challenge studiesAimandampBy inducing higher avidityhigher titer Ab responses to the conserved StalkAvatarandapos s Headless HA immunogen will give rise to broad protection against homologous and drift variantsas well as Groupandampheterologous challengeWe will compare the results obtained with our Group I and II Headless HA immunogens and select a product candidate for preclinical and clinical development Influenza pandemic outbreaks remain an acute threat to world healthand stockpiling a broadly protective influenza vaccine would defend against such a potential catastropheWe propose to confirm that our highly innovative Influenza vaccine immunogen protects against all strains of the Influenza virusincluding pandemic strains Influenzaby specifically triggering the production of antibodies in vaccinated individuals that bind toand inactivate the virus when it enters the body

* Information listed above is at the time of submission. *

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