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Principal Investigator: Jesse Hong-Sae Erasmus
Organization: HDT BIO CORPORATION
Fiscal Year: 2021
Award: $299,976
Funding agency: National Institute of Allergy and Infectious Diseases
Project summary:
First identified in California in 2012, acute flaccid myelitis in children, associated with enterovirus D68 (EV-D68)
infection, has been increasing in incidence with outbreaks detected every 2 years. Enteroviruses are well-known
causes of central nervous system pathologies, ranging from aseptic meningitis to sometimes fatal brainstem
encephalitis and myelitis, which can lead to permanent debilitating paralysis. Additionally, EV-D68 infects the
respiratory tract, causing severe respiratory disease and facilitating person-to-person transmission via
respiratory droplets. Despite EV-D68’s emergence as a major cause of severe respiratory and neurological
disease, there are no vaccines or therapeutics available to combat and control the spread of this pathogen.
HDT Bio has developed a self-amplifying replicon RNA (repRNA) vaccine platform delivered by a Lipid InOrganic
Nanoparticle (LION) scheduled to enter phase I clinical trials in the first quarter of 2021 as a vaccine against
COVID-19. These activities will enable rapid translation of other vaccine candidates, utilizing the same platform,
into the clinic. Additionally, HDT has an ongoing program to develop broad-spectrum anti-EV-D68 antibody
therapeutics, in which we have identified promising RNA-based vaccines that encode the necessary genes for
production of divergent EV-D68 virus like particles (VLPs) in vivo upon intramuscular administration. Our
preliminary data establishes that 1) we can launch VLPs of non-enveloped viruses from our repRNA platform, 2)
we can rapidly adapt this approach for genotypic and/or antigenic variants of EV-D68, and 3) these antigens are
very immunogenic in small and large animals, generating robust neutralizing antibody responses after a single
dose. In this application, we propose to screen six vaccine candidates, which are currently being evaluated as a
mixture in alpacas for antibody discovery efforts, to identify a single candidate that induces the best cross-
neutralizing antibody responses. We will then characterize safety, immunogenicity and efficacy in neurological-
and respiratory-disease mouse models of EV-D68 infection. Finally, we will evaluate safety and immunogenicity
in pregnant mouse models and efficacy in birthed pups while characterizing maternal antibody transfer.
Terms: <0-11 years old><2019-nCoV vaccine><21+ years old><Adult><Adult Human><Alpaca><Animals><Antibodies><Antibody Response><Antigenic Diversity><Antigens><Aseptic Meningitis><Biodistribution><Birth><Brain Inflammation><Brain Stem><Brainstem><CNS Nervous System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 public health crisis><COVID-19 vaccine><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><COVID19 vaccine><CV-19><CV19><California><Central Nervous System><Cerebrospinal Fluid><Child><Child Youth><Children (0-21)><Clinic><Clinical Evaluation><Clinical Testing><Coxsackie Viruses><Coxsackievirus><Cyclic GMP><Data><Developing fetus><Development><Disease Outbreaks><Dose><EC 2.7.7.48><Early-Stage Clinical Trials><Embryo><Embryonic><Encephalitis><Endocarditis><Enterovirus><Enterovirus 68><Enterovirus 71><Enterovirus D68><Evaluation><Evolution><Family><Family Picornaviridae><Fetal Development><Fever><Formulation><Genes><Genetic Alteration><Genetic Change><Genetic defect><Genome><Genotype><Gestation><Guanosine Cyclic Monophosphate><Hepatitis><Human><Human poliovirus><Immunity><Inactivated Vaccines><Inactivated Virus Vaccine><Incidence><Infection><Infection prevention><Inflammatory Myelopathy><Intramuscular><Killed Vaccines><Lead><Licensure><Lipids><Lung diseases><Maternal antibody><Meningitis><Mice><Mice Mammals><Modern Man><Mothers><Murine><Mus><Mutation><Myelitis><Nervous System Diseases><Netherlands><Neuraxis><Neurologic Disorders><Neurological Disorders><Non-Polyadenylated RNA><Outbreaks><Palsy><Paralysed><Parturition><Pathology><Pb element><Persons><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Picornaviridae><Picornaviruses><Plegia><Polio Virus><Poliovirus><Pregnancy><Pregnant Women><Preparation><Prevalence><Prevent infection><Production><Pulmonary Body System><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Organ System><Pyrexia><RNA><RNA Gene Products><RNA Replicase><RNA Viruses><RNA vaccine><RNA-Dependent RNA Polymerase><RNA-Directed RNA Polymerase><RNA-based vaccine><Replication Unit><Replicon><Respiratory Disease><Respiratory System><Respiratory System Disease><Respiratory System Disorder><Respiratory Tracts><Respiratory tract structure><Rhinovirus><Ribonucleic Acid><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV-2 vaccine><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-CoV2 vaccine><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SBIR><Safety><Schedule><Serotyping><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Small Business Innovation Research><Small Business Innovation Research Grant><Spinal Cord Inflammation><Symptoms><Syndrome><Target Populations><Technology><Therapeutic><Therapeutic antibodies><TimeLine><Toxicology><Translations><Transmission><United States><Update><Vaccinated><Vaccination><Vaccines><Variant><Variation><Viral Antibodies><Virus><Virus-like particle><Yeasts><acute flaccid myelitis><adulthood><anti-viral antibody><antibody transfer><antiviral antibody><base><cGMP><cerebral spinal fluid><clinical development><clinical test><combat><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><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 2019 vaccine><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><design><designing><develop a vaccine><development of a vaccine><developmental><disease of the lung><disorder of the lung><efficacy study><expectant mother><expecting mother><febrile><febris><fetal><genome mutation><heavy metal Pb><heavy metal lead><immunogen><immunogenic><immunogenicity><in vivo><lead candidate><lung disorder><mRNA vaccine><mRNA-based vaccine><maternal immunization><maternal vaccination><mouse model><murine model><nano particle><nano-sized particle><nanoparticle><nanosized particle><neonatal mice><neonate><nervous system disorder><neurological disease><neutralizing antibody><paralysis><paralytic><pathogen><phase I protocol><poliomyelitis virus><pregnant><pregnant mothers><programs><pup><recombinant virus><reproductive><research clinical testing><respiratory><respiratory virus><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><spinal fluid><transmission process><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine candidate><vaccine development><vaccine for novel coronavirus><vaccine formulation><viral RNA><virus RNA><virus-like nanoparticles><viruslike particle><youngster>