Recombinant BCG-based SARS-CoV-2 vaccine

Document text

Principal Investigator: Mary  Jackson
Organization: COLORADO STATE UNIVERSITY
Fiscal Year: 2020
Award: $411,968
Funding agency: National Institute of Allergy and Infectious Diseases

Summary
The scale of the humanitarian and economic impact of the COVID-19 pandemic places a high priority on the
development of prophylactic and therapeutic countermeasures to better control SARS-CoV-2 infections. Among
the priorities listed in the NIAID Strategic Plan for COVID-19 research is the need to pursue multiple strategies
to develop a COVID-19 vaccine efficacious across the lifespan, including in the elderly.
Recent epidemiologic studies have highlighted the potential for Mycobacterium bovis BCG (the only approved
vaccine for TB prevention) to mitigate through non-specific immunity the prevalence and severity of the
symptoms of COVID-19. Indeed, BCG vaccination has been known since the 1960s to non-specifically improve
immunity against a number of viral pathogens resulting in reduced morbidity and mortality in neonates, children
and the elderly. Other unique attributes of BCG that make it a vaccine platform of choice for the recombinant
expression of heterologous antigens include the fact that it can produce long-lasting CD4+ and CD8+ T cell
responses, its natural adjuvant properties, its remarkable safety record (> 5 billion doses given to date) and the
fact that it is easy and inexpensive to mass-produce.
The goal of this project is to leverage ongoing COVID-19 research efforts at Colorado State University to
generate recombinant BCG (rBCG) strains expressing SARS-CoV-2 immunogens (Aim 1) and to assess the
immunogenicity and protective efficacy of rBCG in an established animal challenge model of SARS-CoV-2
infection (Aim 2).
We hypothesize that the induction of non-specific immunity against SARS-CoV-2 combined with the adaptive
immune responses elicited by the recombinant expression of validated SARS-CoV-2 antigens will yield rBCG-
based COVID-19 vaccines conferring long-lasting protective immunity in people of all ages. Success in this
approach could rapidly deliver an inexpensive, safe and globally deployable vaccine.

Terms: <0-11 years old><2019 novel coronavirus><2019-nCoV><Adjuvant><Age><Animal Model><Animal Models and Related Studies><Animals><Antibodies><Antigens><Assay><Attention><BCG immunization><BCG vaccination><BCG-vaccinated><Bacille Calmette-Guerin vaccinated><Bacille Calmette-Guerin vaccination><Bacillus><Bacillus Calmette-Guerin vaccination><Bacillus Calmette-Guérin vaccination><Bioassay><Biologic Assays><Biological Assay><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID-19 vaccine><COVID19><COVID19 epidemic><COVID19 pandemic><COVID19 vaccine><Cell model><Cellular model><Child><Child Youth><Children (0-21)><Chimera Protein><Chimeric Proteins><Clinical Trials><Cloning><Colorado><Contracting Opportunities><Contracts><Coronaviridae><Coronavirus><Development><Dose><Elderly><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Feline Coronavirus><Feline Enteric Coronavirus><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Fluorescence Light Microscopy><Fluorescence Microscopy><Funding><Fusion Protein><Genetic><Goals><Golden Hamsters><Golden Syrian Hamsters><Grant><H-D Antigens><Hanganutziu-Deicher Antigens><Heteroantigens><Heterogenetic Antigens><Heterologous Antigens><Heterophil Antigens><Heterophile Antigens><Human><Human Resources><Immunity><Immunization><Immunoblot Analysis><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunostimulation><Individual><Infection><Innate Immunity><Investigators><Laboratories><Length of Life><Location><Longevity><M bovis><M. bovis><MTB vaccine><Manpower><Mesocricetus auratus><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Mycobacterium bovis><Mycobacterium tuberculosis var. bovis><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Paul-Bunnell Antigens><Physiology><Plasmids><Prevalence><Prevention><Production><Property><Public Health><Randomized Controlled Clinical Trials><Reagent><Recombinants><Research><Research Personnel><Research Training><Researchers><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Safety><Severe acute respiratory syndrome coronavirus 2><Severities><Strategic Planning><Symptoms><Syrian Hamsters><T cell response><T8 Cells><T8 Lymphocytes><TB vaccine><Testing><Therapeutic><Tuberculosis Vaccines><United States><United States National Institutes of Health><Universities><Vaccine for TB><Vaccine for Tuberculosis><Vaccines><Virus Replication><Wuhan coronavirus><Xenoantigens><Xenogeneic Antigens><Xenogenic Antigens><adaptive immune response><advanced age><ages><anti-TB vaccine><base><children><childrens'><communicable disease transmission><corona virus><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 epidemic><coronavirus disease 2019 pandemic><coronavirus disease 2019 vaccine><develop a vaccine><development of a vaccine><developmental><disease transmission><economic impact><elders><epidemiologic investigation><epidemiology study><extracellular><flow cytophotometry><geriatric><immunogen><immunogenicity><improved><infectious disease transmission><late life><later life><life span><lifespan><member><model of animal><model organism><mortality><mycobacterial><neonate><older adult><older person><pathogenic virus><personnel><prevent><preventing><programs><prophylactic><protective efficacy><rBCG><recombinant BCG><senior citizen><success><vaccine candidate><vaccine development><vaccine formulation><viral multiplication><viral pathogen><viral replication><virus multiplication><youngster>