Document text
Principal Investigator: Jesse Hong-Sae Erasmus
Organization: HDT BIO CORPORATION
Fiscal Year: 2022
Award: $104,692
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
While a universal influenza vaccine, providing life-long protective immunity against all current and future
drifted and shifted subtypes of influenza virus after 2 or 3 doses, would be a game-changing solution to
reducing the global burden of influenza and its associated morbidity and mortality, other approaches to
solving this problem are urgently needed. There is still much to learn about immune responses to respiratory
pathogens, such as influenza virus, and vaccine approaches that drive life-long immunity to respiratory viruses
have yet to be demonstrated in humans. Therefore, we propose to develop a broadly protective influenza
booster vaccine that can be administered, either seasonally or during pandemics, to individuals with prior
exposures to either natural infection or seasonal vaccination. Given the non-uniform influenza immune history
in a given population of individuals, it is likely that booster vaccines will need to be customized either at the
individual or regional level, based on local influenza virus epidemiology or vaccine uptake. Nucleic acid vaccine
platforms provide the ideal framework for such personalized-medicine approaches, due to the flexibility of
development, as typified by the ongoing COVID-19 pandemic. As proof-of-concept, here we propose to apply
our clinical-stage replicating RNA vaccine platform to develop a booster vaccine targeting the conserved
hemagglutinin stem and nucleoprotein of group 1 influenza viruses and evaluating immunogenicity and
efficacy against heterologous group 1 influenza virus infections in mouse and ferret models of pre-existing
influenza virus immunity. These data will inform the feasibility of such an approach and characterize what
types of pre-existing immunity, in terms of anti-hemagglutinin antibody specificity and magnitude, are
required for booster vaccine efficacy. As these pre-existing antibody criteria are easily assessed in humans, it is
likely that a personalized approach to influenza booster vaccination is achievable.
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disease rate><Murine><Mus><Mutation><Non-Polyadenylated RNA><Non-structural Protein><Nonstructural Protein><Nucleic Acid Vaccines><Nucleoproteins><Orthomyxovirus Type A><Orthomyxoviruses Type B><Pb element><Personalized medical approach><Pharmaceutic Preparations><Pharmaceutical Preparations><Phase><Population><Population Heterogeneity><Problem Solving><Process><Prophylactic vaccination against influenza><RNA><RNA Gene Products><RNA amplification><RNA vaccine><RNA-based vaccine><Reaction Time><Recording of previous events><Response RT><Response Time><Ribonucleic Acid><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SBIR><Safety><Secondary Immunization><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 pandemic><Small Business Innovation Research><Small Business Innovation Research Grant><Specificity><Speed><T cell response><Technology><Time><Type A Influenza><Update><Vaccination><Vaccinee><Vaccines><Variant><Variation><Virus><accept vaccination><accept vaccine><antibody titering><antigen-specific T cells><avian influenza H5N1><avian influenza H5N1 virus><base><booster dose><booster shot><booster vaccination><booster vaccine><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><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 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><deploy vaccines><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><distribute vaccines><diverse populations><driving><drug/agent><epidemiologic><epidemiological><flexibility><flexible><flu immunisation><flu infection><flu serotype><flu strain><flu subtype><flu vaccine><flu viral strain><flu virus infection><flu virus pandemic><flu virus strain><flu virus vaccine><genome mutation><heavy metal Pb><heavy metal lead><heterogeneous population><host response><immune system response><immunogen><immunogenicity><immunoresponse><improved><individualized approach><infected with flu><infected with flu virus><infected with influenza><infected with influenza virus><influenza infection><influenza serotype><influenza strain><influenza subtype><influenza viral strain><influenza virus infection><influenza virus pandemic><influenza virus strain><influenza virus vaccination><influenza virus vaccine><influenzavirus><interest><mRNA vaccine><mRNA-based vaccine><manufacturing process><mortality><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><non-human primate><nonhuman primate><nucleic acid-based vaccine><outcome following vaccination><outcome following vaccine><pandemic><pandemic disease><pandemic flu><pandemic influenza><pandemic preparedness><pandemic strain of influenza><personalization of treatment><personalized approach><personalized medicine><personalized therapy><personalized treatment><population diversity><precision approach><protective efficacy><psychomotor reaction time><public trust><respiratory infection virus><respiratory pathogen><respiratory virus><response><result following vaccination><result following vaccine><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><social role><stem><tailored approach><universal flu vaccine><universal influenza vaccine><universal influenza virus vaccine><universal vaccine against flu><universal vaccine against influenza><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination acceptability><vaccination acceptance><vaccination against influenza><vaccination confidence><vaccination outcome><vaccination result><vaccination uptake><vaccination willingness><vaccine acceptability><vaccine acceptance><vaccine against flu><vaccine against influenza><vaccine confidence><vaccine deployment><vaccine development><vaccine distribution><vaccine efficacy><vaccine outcome><vaccine platform><vaccine result><vaccine roll-out><vaccine rollout><vaccine uptake><vaccine willingness><zoonotic spillover>