Document text
Principal Investigator: Carlos Enrique Catalano
Organization: UNIVERSITY OF COLORADO DENVER
Fiscal Year: 2024
Award: $726,000
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Newly emerging and long-standing infectious challenges, including arboviruses, Ebola virus and pandemic
coronaviruses (CoVs), among others, pose serious public health concerns. Additionally, the potential use of
biological agents as weapons of mass destruction poses an ongoing threat to humanity. All of these issues
have in common the need for development strategies that allow for the rapid design, screening and
formulation of potential vaccine candidates. We have developed a “designer nanoparticle” platform based on
λ phage-like particles, or nanophages (NPs), that can display multiple antigenic biomolecules alone and in
combination in rigorously defined ratios. The NPs can be rapidly modified to screen and evaluate potential
vaccine candidates against newly emerging threats. Herein we propose to develop tools and technologies for
rapid screening of multivalent vaccine candidates effective for current and emerging SARS-CoVs and pre-
emergent SARS-like CoVs. We will engineer “second generation” nanophages (NPs) that display the spike
receptor binding domain (RBD) for these pathogens, the primary target of neutralizing antibody (Ab)
responses. Physiochemical and structural characterization of the preparations will be employed to ensure
that they possess properties that are appropriate for a pharmaceutical preparation. We will also employ a
novel atomic layer deposition technology to generate thermostable, timed-release, single-shot vaccine
formulations that reduce or eliminate onerous “cold-chain” requirements for their distribution. We further
propose to determine the immunogenicity and protective capacity of mosaic NPs engineered to
simultaneously display multiple antigens. These studies will identify vaccine candidates that elicit potent,
durable, and broad neutralizing Ab and T cell responses and protective immunity against SARS-CoV-2
variants and pre-emergent SARS-like bat CoVs. In addition to developing this powerful platform and
implementing novel formulation strategies, these studies will help define mechanisms of immunogenicity and
develop a platform for the rapid engineering of vaccine candidates for existing and untoward emerging
biological threats. In sum, this application seeks to provide compelling evidence that the nanophage system
provides a platform for facile and rapid generation, and formulation of highly active multi-antigen presenting
vaccines.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV variant><2019-nCoV variant forms><2019-nCoV variant strains><Address><Antibodies><Antibody Response><Antigen Presentation><Antigens><Arboviral><Arboviruses><Area><Arthropod-Borne Viruses><Avidity><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bacteriophages><Bats><Biological><Biological Agent><Biological Products><CHIKV><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 immunity><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 variant><COVID-19 variant forms><COVID-19 variant strains><COVID-19 virus><COVID-19 years><COVID19 virus><Chikungunya virus><Chiroptera><CoV-2><CoV2><Cold Chains><Coronaviridae><Coronavirus><Data><Development><Disease><Disorder><Dose><Drugs><EBOV><Ebola virus><Ebola-like Viruses><Engineering><Formulation><Future><Generations><Goals><Health><Humanities><Immunize><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Infection><Influenza Virus><Intramuscular><Libraries><Ligands><MERS corona virus><MERS coronavirus><MERS virus><MERS-CoV><Medication><Memory><Mice><Mice Mammals><Middle East Respiratory Syndrome Corona Virus><Middle East Respiratory Syndrome Coronavirus><Middle East Respiratory Syndrome Virus><Middle East Respiratory Syndrome-CoV><Middle East Respiratory Virus><Middle East Respiratory coronavirus><Middle Eastern Respiratory Syndrome Corona virus><Middle Eastern Respiratory Syndrome Coronavirus><Middle Eastern Respiratory Syndrome Virus><Middle Eastern Respiratory Syndrome-CoV><Molecular Configuration><Molecular Conformation><Molecular Stereochemistry><Morbidity><Morbidity - disease rate><Murine><Mus><Outcome><Paramyxoviridae><Paramyxovirus><Pathogenicity><Pathologic><Phages><Pharmaceutical Preparations><Polymers><Polynucleotides><Preparation><Property><Proteins><Public Health><Publishing><RNA vaccine><RNA-based vaccine><Rapid screening><SARS><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS coronavirus disease><SARS-Associated Coronavirus><SARS-CO-V2><SARS-COVID-2><SARS-CoV><SARS-CoV disease><SARS-CoV-1><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 immunity><SARS-CoV-2 pandemic><SARS-CoV-2 variant><SARS-CoV-2 variant forms><SARS-CoV-2 variant strains><SARS-CoV2><SARS-Related Coronavirus><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><Severe Acute Respiratory Coronavirus><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV disease><Severe Acute Respiratory Syndrome Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><Severe Acute Respiratory Syndrome coronavirus disease><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 immunity><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Surface><System><T cell response><Technology><Testing><Vaccines><Variant><Variation><Viral><Virus><Wuhan coronavirus><ZIKV><Zika Virus><atomic layer deposition><bacterial virus><biologic><biologics><biopharmaceutical><biotherapeutic agent><conformation><conformational><conformational state><conformationally><conformations><corona virus><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 immunity><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 variant><coronavirus disease 2019 variant forms><coronavirus disease 2019 variant strains><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><coronavirus of pandemic concern><coronavirus of pandemic potential><coronavirus vaccine><coronavirus with pandemic potential><deploy vaccines><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><distribute vaccines><drug/agent><emerging pathogen><evaluate vaccines><full scale manufacturing><hCoV19><immunity against COVID-19><immunity against SARS-CoV-2><immunity against Severe acute respiratory syndrome coronavirus 2><immunity against coronavirus disease 2019><immunity to COVID-19><immunity to SARS-CoV-2><immunity to Severe acute respiratory syndrome coronavirus 2><immunity to coronavirus disease 2019><immunogen><immunogenicity><influenzavirus><lambda like Viruses><lambda-Like Phages><large scale manufacturing><large scale production><mRNA vaccine><mRNA-based vaccine><macromolecule><mass production><mortality><mosaic><nCoV2><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><new pathogen><novel><novel pathogen><pandemic coronavirus><pandemic threat coronavirus><particle><pathogen><polymer><polymeric><preparations><protective efficacy><receptor binding><receptor bound><response><screening><screenings><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 variant><severe acute respiratory syndrome coronavirus 2 variant forms><severe acute respiratory syndrome coronavirus 2 variant strains><severe acute respiratory syndrome-CoV><stem><thermolability><thermostability><tool><vaccine against coronavirus><vaccine candidate><vaccine candidate against coronavirus><vaccine deployment><vaccine development><vaccine distribution><vaccine evaluation><vaccine formulation><vaccine platform><vaccine roll-out><vaccine rollout><vaccine screening><vaccine testing><virtual><weapons of mass destruction><zikav>