UCLA researchers in the School of Medicine have developed a novel single-vector platform vaccine for preventing melioidosis, an infection caused by Burkholderia pseudomallei.
BACKGROUND: Melioidosis, also known as Whitmore’s disease, is an infectious disease that can infect both humans and animals. The bacterium Burkholderia pseudomallei (Bp) is responsible for the disease and is found in contaminated soil and water, especially in tropical areas. Although this disease is predominant in Southeast Asia and northern Australia, the bacterium has been identified in Mississippi, Puerto Rico and the U.S. Virgin Islands. In total, the disease accounts for an estimated 165,000 cases and 89,000 deaths per year. Additionally, Bp is categorized as a potential bioweapon and Tier 1 Select Agent by the Centers for Disease Control and Prevention (CDC), as inhalation of low doses of Bp can result in rapidly fatal pneumonia. This is a great health concern as melioidosis is not only difficult to diagnose, but it is difficult to treat due to its resistance to most conventional antibiotics. There is no licensed vaccine against melioidosis.
INNOVATION: UCLA researchers led by Dr. Marcus Horwitz have developed a single vector platform vaccine for the prevention of melioidosis that is suitable for use in both humans and animals. The vaccine is built upon their previously developed LVS ΔcapB vector, a live attenuated capB mutant of the widely used tularemia vaccine known as Live Vaccine Strain (LVS), which has been administered to over 60 million people. Even before the major attenuating capB mutation, the parental LVS vaccine had two major attenuating deletions and several minor mutations of its bacterial parent. The melioidosis vaccine, which expresses several highly immunogenic Bp proteins, can be administered intradermally or by multiple other routes, e.g. subcutaneously, intramuscularly, intranasally, inhaled, or even orally to a mammalian host. Even a single dose has demonstrated high efficacy against lethal respiratory challenge in a rigorous and highly sensitive animal model. The developed vaccine is cost-effective, does not contain animal products, does not need an adjuvant, and has the ease of rapid large-scale manufacturing.
POTENTIAL APPLICATIONS:
- Vaccine for Burkholderia pseudomallei for both humans and animals
ADVANTAGES:
- Simplified regulatory approval
- Can be administered with other vaccines using the same vector including vaccines against the Tier 1 select agent diseases tularemia, anthrax and plague
- No need for animal products, adjuvants
- Multiple routes of administration
- Low toxicity
DEVELOPMENT-TO-DATE: In vivo validation in relevant highly sensitive mouse models show that the vaccines are safe and highly protective against lethal respiratory challenge.
Related Papers (from the inventors only):
Jia, Q., R. Bowen, R., B-Y. Lee, B.J. Dillon, S. Masleša-Galić, and M.A. Horwitz. 2016. Francisella tularensis Live Vaccine Strain deficient in capB and overexpressing the fusion protein of IglA, IglB, and IglC from the bfr promoter induces improved protection against F. tularensis respiratory challenge. Vaccine 34:4969-4978. doi: 10.1016/j.vaccine.2016.08.041.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028307/
Jia, Q., R. Bowen, B.J. Dillon, S. Masleša-Galić, B.T. Chang, A.C. Kaidi, and M.A. Horwitz. 2018. Single vector platform vaccine protects against lethal respiratory challenge with Tier 1 select agents of anthrax, plague, and tularemia. Scientific Reports 8:7009. May 3, 2018.
doi: 10.1038/s41598-018-24581-y
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934503/?report=classic
Jia, Q., H. Bielefeldt-Ohmann, R. M. Maison, S. Masleša-Galić, S.K. Cooper, R. A. Bowen and M.A. Horwitz. 2020/2021. Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters. [bioRxiv, doi:10.1101/2020.11.17.387555 (2020)]. NPJ Vaccines (2021) 6:47. Epub 2021-03-30.
doi: 10.1038/s41541-021-00321-8. https://rdcu.be/chKwi
Jia, Q., H. Bielefeldt-Ohmann, R. M. Maison, A. Hartwig, S. Masleša-Galić, R. A. Bowen and M.A. Horwitz. 2022. Oral administration of universal bacterium-vectored COVID-19 vaccine protects against severe COVID-19-like disease in Syrian hamsters. Microbiology Spectrum EPub: March 14, 2023. doi: 10.1128/spectrum.05035-22.
https://doi.org/10.1128/spectrum.05035-22
Mlynek, K.D., C.R. Cline, S.S. Biryukov, R.G. Toothman, B.A. Bachert, C.P. Klimko, J.L. Shoe, M. Hunter, Z.M. Hedrick, J.L. Dankmeyer, S. Mou, D. Fetterer, J. Qui, E.D. Lee; C.K. Cote, Q. Jia, M.A. Horwitz and J.A. Bozue. 2023. The rLVS ΔcapB/iglABC vaccine provides potent protection in Fischer rats against inhalational tularemia caused by various virulent Francisella tularensis strains. Human Vaccines & Immunotherapeutics19(3):2277083. Epub 2023-11-17. doi: 10.1080/21645515.2023.2277083. https://doi.org/10.1080/21645515.2023.2277083
Tullius, M.V., R. A. Bowen, P.S. Back, S. Masleša-Galić, S. Nava, and M.A. Horwitz. 2023. LVS ΔcapB-vectored multiantigenic melioidosis vaccines protect against lethal respiratory Burkholderia pseudomallei challenge in highly sensitive BALB/c mice. In press.