LVS Δ capB -vectored multiantigenic melioidosis vaccines protect against lethal respiratory Burkholderia pseudomallei challenge in highly sensitive BALB/c mice

Article

Author: Bowen, Richard A ; Tullius, Michael V ; Nava, Susana ; Masleša-Galić, Saša ; Horwitz, Marcus A ; Back, Peter S

ABSTRACT Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent Burkholderia pseudomallei (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine against melioidosis exists. In preclinical vaccine studies, demonstrating protection against respiratory infection in the highly sensitive BALB/c mouse has been especially challenging. To address this challenge, we have used a safe yet potent live attenuated platform vector, LVS Δ capB , previously used successfully to develop vaccines against the Tier 1 select agents of tularemia, anthrax, and plague, to develop a melioidosis vaccine. We have engineered melioidosis vaccines (rLVS Δ capB /Bp) expressing multiple immunoprotective Bp antigens among type VI secretion system proteins Hcp1, Hcp2, and Hcp6, and membrane protein LolC. Administered intradermally, rLVS Δ capB /Bp vaccines strongly protect highly sensitive BALB/c mice against lethal respiratory Bp challenge, but protection is overwhelmed at very high challenge doses. In contrast, administered intranasally, rLVS Δ capB /Bp vaccines remain strongly protective against even very high challenge doses. Under some conditions, the LVS Δ capB vector itself provides significant protection against Bp challenge, and consistent with this, both the vector and vaccines induce humoral immune responses to Bp antigens. Three-antigen vaccines expressing Hcp6-Hcp1-Hcp2 or Hcp6-Hcp1-LolC are among the most potent and provide long-term protection and protection even with a single intranasal immunization. Protection via the intranasal route was either comparable to or statistically significantly better than the single-deletional Bp mutant Bp82, which served as a positive control. Thus, rLVS Δ capB /Bp vaccines are exceptionally promising safe and potent melioidosis vaccines. IMPORTANCE Melioidosis, a major neglected disease caused by the intracellular bacterial pathogen Burkholderia pseudomallei , is endemic in many tropical areas of the world and causes an estimated 165,000 cases and 89,000 deaths in humans annually. Moreover, B. pseudomallei is categorized as a Tier 1 select agent of bioterrorism, largely because inhalation of low doses can cause rapidly fatal pneumonia. No licensed vaccine is available to prevent melioidosis. Here, we describe a safe and potent melioidosis vaccine that protects against lethal respiratory challenge with B. pseudomallei in a highly sensitive small animal model—even a single immunization is highly protective, and the vaccine gives long-term protection. The vaccine utilizes a highly attenuated replicating intracellular bacterium as a vector to express multiple key proteins of B. pseudomallei ; this vector platform has previously been used successfully to develop potent vaccines against other Tier 1 select agent diseases including tularemia, anthrax, and plague.

18 Aug 2022·Infection and Immunity

Development of Melioidosis Subunit Vaccines Using an Enzymatically Inactive Burkholderia pseudomallei AhpC

Article

Author: Khakhum, Nittaya ; Torres, Alfredo G. ; Shaffer, Teresa L. ; Schmidt, Lindsey K. ; Brett, Paul J. ; Wilson, Shane M. ; Burtnick, Mary N. ; Orne, Caitlyn E.

Burkholderia pseudomallei , the causative agent of melioidosis, is a facultative intracellular, Gram-negative pathogen that is highly infectious via the respiratory route and can cause severe, debilitating, and often fatal diseases in humans and animals. At present, no licensed vaccines for immunization against this CDC Tier 1 select agent exist.

01 Dec 2019·BMC MedicineQ1 · MEDICINE

The global impact and cost-effectiveness of a melioidosis vaccine

Q1 · MEDICINE

ArticleOA

Author: Flasche, Stefan ; Limmathurotsakul, Direk ; Dance, David A B ; Titball, Richard ; Atkins, Tim ; Jit, Mark ; Luangasanatip, Nantasit ; Currie, Bart J ; Mukhopadhyay, Chiranjay

BACKGROUNDEvery year, 90,000 people may die from melioidosis. Vaccine candidates have not proceeded past animal studies, partly due to uncertainty around the potential market size. This study aims to estimate the potential impact, cost-effectiveness and market size for melioidosis vaccines.METHODSAge-structured decision tree models with country-specific inputs were used to estimate net costs and health benefits of vaccination, with health measured in quality-adjusted life years (QALYs). Four target groups of people living in endemic regions were considered: (i) people aged over 45 years with chronic renal disease, (ii) people aged over 45 years with diabetes, (iii) people aged over 45 years with diabetes and/or chronic renal disease, (iv) everyone aged over 45 years. Melioidosis risk was estimated using Bayesian evidence synthesis of 12 observational studies. In the base case, vaccines were assumed to have 80% efficacy, to have 5-year mean protective duration and to cost USD10.20-338.20 per vaccine.RESULTSVaccination could be cost-effective (with incremental cost-effectiveness ratio below GDP per capita) in 61/83 countries/territories with local melioidosis transmission. In these 61 countries/territories, vaccination could avert 68,000 lost QALYs, 8300 cases and 4400 deaths per vaccinated age cohort, at an incremental cost of USD59.6 million. Strategy (ii) was optimal in most regions. The vaccine market may be worth USD268 million per year at its threshold cost-effective price in each country/territory.CONCLUSIONSThere is a viable melioidosis vaccine market, with cost-effective vaccine strategies in most countries/territories with local transmission.

100 Deals associated with Melioidosis Vaccine(Third Military Medical University)

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Indication	Highest Phase	Country/Location	Organization	Date
Melioidosis	Preclinical	CN	Xinqiao Hospital	23 Dec 2022

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