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Principal Investigator: Albert J. Auguste
Organization: VIRGINIA POLYTECHNIC INST AND ST UNIV
Fiscal Year: 2023
Award: $262,294
Funding agency: National Institute of Allergy and Infectious Diseases
Abstract
Orthobunyaviruses are an understudied genus in the order Bunyavirales that has no vaccines or therapies in
clinical development. One of the prototype pathogens within this genus, as recently identified by NIAID, is Cache
Valley virus (CVV). CVV is an emerging arthropod-borne virus that induces spontaneous abortions and
congenital malformations in ruminants and humans. Given CVV’s prevalence and its broad host range, coupled
with the expanding geographical range of its diverse array of competent vectors, the epidemic potential of CVV
continues to increase, reminiscent of what was previously observed for Chikungunya and Zika viruses. To date,
there have been no reported vaccine development activities for this virus, and prototype approaches are urgently
needed to develop road maps for vaccines against viruses within this genus should an epidemic occur in the
future. With the rapid adoption of mRNA vaccine technology during the ongoing COVID-19 pandemic, coupled
with the recent emergency use approval of HDT Bio’s self-amplifying mRNA vaccine platform, we propose to
apply HDT’s technology to develop prototype vaccines for the orthobunyavirus genus with a proof-of-concept
vaccine to prevent CVV infection in a novel murine model of CVV infection and disease. This innovative, timely,
and critically important R21 aims to study the safety profile and protective efficacy of this vaccine, and identify
the important antigens required for broad cross-reactive immunity post-vaccination, via two specific aims:
1. Evaluate the safety, immunogenicity, and optimal dosage regimen for a LIONTM-formulated, replicon-
RNA vaccine for CVV.
2. Investigate the efficacy and correlates of protection of a LION-formulated, replicon-RNA vaccine for
preventing CVV-induced disease in murine models.
Considering a One Health approach, and recognizing the connection between the health of humans and animals,
such a vaccine could have an immediate impact in the veterinary/agricultural market, simultaneously preventing
economic damage, animal disease, and disease emergence in humans. In the event of epidemic emergence in
humans, this approach could be rapidly adapted and scaled for human trials.
Terms: <Adoption><Advisory Committees><Agriculture><Animal Diseases><Animals><Antibodies><Antigens><Arboviral><Arboviruses><Arthropod-Borne Viruses><Birth Defects><Brain Inflammation><Brazil><Bunyavirales><Bunyavirus><CHIKV><COVID crisis><COVID epidemic><COVID pandemic><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><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><Cache Valley virus><Case Study><Categories><Cephalalgia><Cephalgia><Cephalodynia><Cessation of life><Characteristics><Chikungunya virus><Chronic><Clinical><Clinical Trials><Collaborations><Congenital Abnormality><Congenital Anatomic Abnormality><Congenital Anatomical Abnormality><Congenital Defects><Congenital Deformity><Congenital Malformation><Coupled><Coupling><Cranial Pain><Culicidae><Death><Disease><Disorder><Dose><Economic Burden><Economics><Emergencies><Emergency Situation><Encephalitis><Epidemic><Event><Farm Animal><Fatigue><Fever><Food><Future><Genus Phlebovirus><Geographic Distribution><Geography><Goals><Head Pain><Headache><Health><Health protection><High Prevalence><History><Human><Immune response><Immunity><Immunization><Immunocompetent><Immunological response><Immunologist><In Vitro><Incidence><India><Induced Abortion><Infant><Infection><Lack of Energy><Length of Life><Licensing><Lipids><Livestock><Longevity><Macrocephaly><Maps><Marketing><Medical><Megacephaly><Megalocephaly><Meningitis><Miscarriage><Modern Man><Morbidity><Morbidity - disease rate><Mosquitoes><Musculoskeletal System><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Nausea><Neurologic><Neurological><Non-Polyadenylated RNA><North America><Orthobunyavirus><Pathogenesis><Phenotype><Phlebovirus><Position><Positioning Attribute><Prevalence><Prevention><Pyrexia><RNA><RNA Gene Products><RNA Viruses><RNA vaccine><RNA-based vaccine><Recording of previous events><Regimen><Replication Unit><Replicon><Reporting><Republic of Korea><Research Resources><Resources><Ribonucleic Acid><Rift Valley fever virus><Risk><Role><Ruminantia><Ruminants><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><Safety><Seroprevalences><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><South Korea><Spontaneous abortion><Study models><System><T cell response><Task Forces><Technology><Teratogenic><Teratogenicity><Teratogens><Testing><Transmission><United States National Institutes of Health><VEE virus><VEEV><Vaccination><Vaccines><Venezuelan Equine Encephalitic Virus><Venezuelan Equine Encephalitis Virus><Venezuelan Equine Encephalomyelitis Virus><Viral><Viral Antigens><Viral Diseases><Viral Pathogenesis><Virus><Virus Diseases><Virus Replication><ZIKV><Zika Virus><Zoonoses><Zoonotic><Zoonotic Infection><advisory team><agricultural><artificial abortion><burden of disease><burden of illness><case report><clinical development><combat><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><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 global pandemic><coronavirus disease-19 pandemic><cross reactivity><develop a vaccine><develop vaccines><development of a vaccine><disease burden><dosage><economic><enzootic><epidemic concern><epidemic potential><epidemic risk><epidemic threat><epizootic><febrile><febris><future epidemic><head ache><histories><host response><human pathogen><immune competent><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><in vivo><innovate><innovation><innovative><life span><lifespan><locomotor system><mRNA vaccine><mRNA-based vaccine><member><mortality><mouse model><murine model><nano particle><nano-sized particle><nanoparticle><nanosized particle><next epidemic><novel><pathogen><pre-clinical development><pre-clinical evaluation><preclinical development><preclinical evaluation><prevent><preventing><protective efficacy><prototype><response><safety study><sandfly fever virus group><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><social role><transmission process><vaccination study><vaccination trial><vaccine candidate><vaccine development><vaccine efficacy><vaccine platform><vaccine study><vaccine trial><vaccinology><vector><viral infection><viral multiplication><viral replication><virus antigen><virus infection><virus multiplication><virus pathogenesis><virus-induced disease><years of life lost to disability><years of life lost to disease><zikav>