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Principal Investigator: Barton F. Haynes
Organization: DUKE UNIVERSITY
Fiscal Year: 2021
Award: $1,904,954
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT - Project 3
Coronaviruses havethe potential to cause significant morbidity andmortality as demonstrated by the ongoing
SARS-CoV-2 pandemic. The purpose of this program project is to develop safe and broadly-protective group 2b
and 2c betacoronavirus (panbetaCoV) vaccines capable of inducing protective immune responses and evaluate
them in animal challenge models. The fact that there has been 3 major CoV outbreaks (SARS-CoV-1, MERS
and SARS-CoV-2) in less than 20 years strongly supports the idea of generation of broadly protective
panbetaCoV vaccines that can significantly contribute to global pandemic preparedness against future CoV
epidemics and pandemics. Coronaviruses (CoVs) have significant pandemic potential, as illustrated by the
outbreaks of SARS-CoV-1, MERS and SARS-CoV-2 in less than 20 years. The outbreak of a novel CoV, SARS-
CoV-2, has resulted in at over 85 million infections and 1.8 million deaths. Thus, development of panbetaCoV
vaccines is essential to preventing a future outbreaks due to an emerging new zoonotic CoV.
Messenger RNA/LNP-based vaccines have proved to be highly effective against cancer and infectious
diseases and one of the most effective platforms comprises nucleoside-modified mRNA (mod mRNA)
encapsulated in LNPs. Two of the leading COVID-19 vaccines in phase 3 clinical trials by Moderna and
Pfizer/BioNTech use our nucleoside-modified mRNA-LNP vaccine platform and are 95% protective in Phase 3
trials. Besides potency, mRNA/LNPs can undergo rapid, scalable production and induced durable immune
responses. In Project 3, we propose to develop cross-protective and safe mod mRNA-LNP vaccines against
animal and human betaCoVs and evaluate their immunogenicity and protective efficacy in preclinical studies.
We hypothesize that mod mRNA-LNP vaccines encoding CoV immunogens capable of inducing broadly
protective and broadly cross-protective B and T cell responses will effectively provide protection against future
outbreaks of zoonotic CoVs.. We propose the following Specific Aims:
Aim 1) Development of neutralizing antibody panbetaCoV vaccines using mod mRNA-LNP.
Aim 2) Development of T cell vaccines using mod mRNA-LNP.
In summary, this proposal aims to develop panbetaCoV vaccines that are safe, easy-to-produce and can
induce protective immune responses in animal challenge models. The data generated will be capable of moving
this panbetaCoV vaccine approach to clinical development.
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disease rate><Nucleosides><Outbreaks><Pathology><Phase 3 Clinical Trials><Phase III Clinical Trials><Pre-Clinical Model><Preclinical Models><Production><Proteins><Pulmonary Pathology><Risk><SARS Virus><SARS corona virus><SARS corona virus 2><SARS coronavirus><SARS-Associated Coronavirus><SARS-CoV><SARS-CoV-2><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><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-CoV2 vaccine><SARS-Related Coronavirus><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><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 CoV 2><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 Virus><Severe Acute Respiratory Syndrome corona virus><Severe Acute Respiratory Syndrome coronavirus><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 corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Structure of germinal center of lymph node><Surface Proteins><Syrian Hamsters><T cell response><T-Cell Development><T-Cell Ontogeny><T-Cells><T-Lymphocyte><T-Lymphocyte Development><Teff cell><Testing><Vaccines><Viral><Viral Diseases><Virus><Virus Diseases><Wuhan coronavirus><ZIKV><Zika Virus><advanced age><ages><base><beta CoV><beta coronavirus><beta coronavirus vaccine><betaCoV><betacoronavirus><betacoronavirus vaccine><clinical development><clinical test><corona virus><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><corona virus disease 2019 vaccine><corona virus emergence><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 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus emergence><design><designing><developmental><ebolavirus><effector T cell><elders><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><env Antigens><env Gene Products><env Polyproteins><env Protein><expectation><flexibility><flexible><geriatric><hCoV19><herpes simplex ii><host response><human alphaherpesvirus 2><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><influenzavirus><innovate><innovation><innovative><late life><later life><lipid nanoparticle><lung pathology><mRNA><malignancy><model of animal><model organism><mortality><mouse model><murine model><nCoV><nCoV2><nano particle><nano-sized particle><nanoparticle><nanosized particle><neoplasm/cancer><neutralizing antibody><new CoV><new corona virus><new coronavirus><new vaccines><next generation vaccines><novel CoV><novel corona virus><novel coronavirus><novel vaccines><older adult><older person><panbetaCoV vaccine><pandemic><pandemic disease><pandemic preparedness><particle><pathogen><pathogenic virus><phase 3 trial><phase III protocol><phase III trial><pre-clinical study><preclinical study><prevent><preventing><programs><protective efficacy><receptor binding><receptor bound><research clinical testing><response><senior citizen><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome-CoV><thymus derived lymphocyte><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 antibodies><vaccine candidate><vaccine for novel coronavirus><vaccine induced antibodies><vaccine-induced antibodies><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease><zikav><zoonotic CoV><zoonotic coronavirus><β CoV><β coronavirus><β coronavirus vaccine><βCoV>