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The autotransporter protein BatA is a protective antigen against lethal aerosol infection with Burkholderia mallei and Burkholderia pseudomallei
- Source :
- Vaccine: X, Vol 1, Iss, Pp-(2019), Vaccine: X
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Background: Burkholderia mallei and Burkholderia pseudomallei are the causative agents of glanders and melioidosis, respectively. There is no vaccine to protect against these highly-pathogenic and intrinsically antibiotic-resistant bacteria, and there is concern regarding their use as biological warfare agents. For these reasons, B. mallei and B. pseudomallei are classified as Tier 1 organisms by the U.S. Federal Select Agent Program and the availability of effective countermeasures represents a critical unmet need. Methods: Vaccines (subunit and vectored) containing the surface-exposed passenger domain of the conserved Burkholderia autotransporter protein BatA were administered to BALB/c mice and the vaccinated animals were challenged with lethal doses of wild-type B. mallei and B. pseudomallei strains via the aerosol route. Mice were monitored for signs of illness for a period of up to 40 days post-challenge and tissues from surviving animals were analyzed for bacterial burden at study end-points. Results: A single dose of recombinant Parainfluenza Virus 5 (PIV5) expressing BatA provided 74% and 60% survival in mice infected with B. mallei and B. pseudomallei, respectively. Vaccination with PIV5-BatA also resulted in complete bacterial clearance from the lungs and spleen of 78% and 44% of animals surviving lethal challenge with B. pseudomallei, respectively. In contrast, all control animals vaccinated with a PIV5 construct expressing an irrelevant antigen and infected with B. pseudomallei were colonized in those tissues. Conclusion: Our study indicates that the autotransporter BatA is a valuable target for developing countermeasures against B. mallei and B. pseudomallei and demonstrates the utility of the PIV5 viral vaccine delivery platform to elicit cross-protective immunity against the organisms. Keywords: Glanders, Melioidosis, Lethal aerosol challenge, PIV5 vaccine vector, Tier 1 select agent, Autotransporter protective antigen
- Subjects :
- Tier 1 select agent
Autotransporter protective antigen
lcsh:Immunologic diseases. Allergy
PIV5 vaccine vector
Melioidosis
Microbiology
03 medical and health sciences
Burkholderia mallei
medicine
Lethal aerosol challenge
030304 developmental biology
2. Zero hunger
0303 health sciences
General Veterinary
General Immunology and Microbiology
biology
030306 microbiology
Burkholderia pseudomallei
Viral Vaccine
Glanders
Public Health, Environmental and Occupational Health
biology.organism_classification
medicine.disease
bacterial infections and mycoses
3. Good health
Vaccination
Infectious Diseases
Burkholderia
Regular paper
Autotransporter domain
Molecular Medicine
bacteria
lcsh:RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 25901362
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Vaccine: X
- Accession number :
- edsair.doi.dedup.....89479cd1b66484e955400ef873e4af9f