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Principal Investigator: KENT E. KESTER
Organization: INTERNATIONAL AIDS VACCINE INITIATIVE
Fiscal Year: 2023
Award: $422,266
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
Tuberculosis remains one of the top ten leading causes of death worldwide (1). Based on the most current
information from WHO 2020 report, in 2019 an estimated 1.4 million people died from TB and approximately
10,000,000 fell ill (2). The COVID-19 pandemic has led to massive decreases in TB case identification and Stop
TB estimates an additional 1.4 million TB deaths will be registered over the next 4 years (3, 4). This, together
with the growing threat of drug-resistant TB and the co-epidemics of TB with HIV and diabetes makes ending
the TB epidemic more crucial than ever before. A vaccine that prevents adolescents and adults from acquiring,
developing, and transmitting TB would be the single most cost-effective tool in ending the TB epidemic (5).
The TuBerculosis Vaccine Initiative (TBVI) and Treatment Action Group (TAG) TB Vaccine Pipelines report
twelve subunit vaccines including recombinant protein/adjuvant and viral vector vaccines spanning from
preclinical through Phase 3 development (6, 7). Of these, nine include Ag85 (Ag85A or B) and six include
ESAT6. The highly limited antigenic and immunological diversity present in the pipeline is a significant gap in
efforts to develop a novel, effective vaccine. The proposed research is intended to bring needed antigenic and
platform diversity to the pre-clinical TB vaccine pipeline using Moderna’s cutting-edge mRNA vaccine
technology and expertise.
Within the R61 phase of this program, we will first optimize mycobacterial antigen sequences for expression in
mammalian cells using Moderna’s proprietary learnings and algorithms. These principles will be applied to the
development of three candidate mRNA vaccines, including 1) an antigen cassette previously shown to induce
protection in animal models when delivered as a protein plus adjuvant, 2) a new antigen cassette
including novel antigens, and 3) the M72 antigen shown to induce protection in humans when delivered as
recombinant protein with the AS01E adjuvant. We will then use data from murine immunogenicity and protection
studies to select the two best candidates for advancement into the R33 phase. Within the R33 phase, we will
use the guinea pig challenge model to downselect to a final lead candidate for further advancement. Once a final
lead candidate is selected, additional studies will be conducted to further characterize the candidate, including
protection in genetically diverse mice and an immunogenicity study in nonhuman primates to optimize the
vaccination regimen for clinical use.
By the end of this program, we will have a novel lead vaccine candidate ready for advancement into IND-
enabling studies and early development as a vaccine to prevent TB disease in adults and adolescents.
Terms: <21+ years old><AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adjuvant><Adolescent><Adolescent Youth><Adult><Adult Human><Algorithms><Animal Model><Animal Models and Related Studies><Animals><Antigenic Diversity><Antigens><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><COVID19><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 public health crisis><CV-19><CV19><Cause of Death><Cavia><Cessation of life><Clinical><Clinical Trials><Codon><Codon Nucleotides><Communicable Diseases><Data><Data Set><Death><Development><Development and Research><Diabetes Mellitus><Disease><Disorder><Dose><Drug Resistance Tuberculosis><Drug Resistant TB><Drug Resistant Tuberculosis><Drug resistance in tuberculosis><Early-Stage Clinical Trials><Epidemic><Evaluation><Generations><Goals><Guinea Pigs><Guinea Pigs Mammals><HIV><Head><Human><Human Immunodeficiency Viruses><Incidence><Individual><Infectious Agent><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><LAV-HTLV-III><Lead><Learning><Lymphadenopathy-Associated Virus><M tb><M tuberculosis><M tuberculosis antigen><M tuberculosis infection><M. tb><M. tb infection><M. tuberculosis><M. tuberculosis antigen><M. tuberculosis infection><M.tb antigen><M.tb infection><M.tuberculosis infection><MTB infection><MTB vaccine><Mammalian Cell><Messenger RNA><Metabolic Glycosylation><Mice><Mice Mammals><Modeling><Modern Man><Modification><Mtb antigen><Murine><Mus><Mycobacterium tuberculosis><Mycobacterium tuberculosis (MTB) infection><Mycobacterium tuberculosis antigens><Mycobacterium tuberculosis infection><Pb element><Persons><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Phase I Study><Position><Positioning Attribute><Proteins><Public Health><R & D><R&D><RNA vaccine><RNA-based vaccine><Recombinant Proteins><Regimen><Reporting><Research><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><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><Subunit Vaccines><Sustainable Development><TB drug resistance><TB infection><TB vaccine><Technology><Time><Transmission><Tuberculosis><Tuberculosis Vaccines><United Nations><Vaccination><Vaccine for TB><Vaccine for Tuberculosis><Vaccines><Viral Vector><Virus-HIV><adulthood><anti-TB vaccine><clinical development><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><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 crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus infectious disease-19><cost effective><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><diabetes><disseminated TB><disseminated tuberculosis><drug resistance in TB><drug resistant in tuberculosis><glycosylation><heavy metal Pb><heavy metal lead><immunogen><immunogenicity><immunological diversity><infection due to Mycobacterium tuberculosis><infectious organism><innovate><innovation><innovative><juvenile><juvenile human><lead candidate><mRNA><mRNA vaccine><mRNA-based vaccine><model of animal><mtb><mycobacterial><new approaches><new vaccines><next generation vaccines><non-Native><non-human primate><nonhuman primate><nonnative><novel><novel approaches><novel strategies><novel strategy><novel vaccines><pandemic><pandemic disease><phase 1 study><phase I protocol><plasmid vaccine><pre-clinical><preclinical><prevent><preventing><product development><programs><research and development><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><tool><transmission process><tuberculosis infection><tuberculous spondyloarthropathy><vaccine candidate><vaccine development><vector vaccine>