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Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle (VLP)-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
Protective antigens against glanders identified by expression library immunization
Gregory C Whitlock1, Mark D Robida, Barbara M Judy
1Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, TX, USA.
Abstract:
Burkholderia are highly evolved Gram-negative bacteria that primarily infect solipeds but are transmitted to humans by ingestion and cutaneous or aerosol exposures. Heightened concern over human infections of Burkholderia mallei and the very closely related species B. pseudomallei is due to the pathogens' proven effectiveness as bioweapons, and to the increased potential for natural opportunistic infections in the growing diabetic and immuno-compromised populations. These Burkholderia species are nearly impervious to antibiotic treatments and no vaccine exists. In this study, the genome of the highly virulent B. mallei ATCC23344 strain was examined by expression library immunization for gene-encoded protective antigens. This protocol for genomic-scale functional screening was customized to accommodate the unusually large complexity of Burkholderia, and yielded 12 new putative vaccine candidates. Five of the candidates were individually tested as protein immunogens and three were found to confer significant partial protection against a lethal pulmonary infection in a murine model of disease. Determinations of peripheral blood cytokine and chemokine profiles following individual protein immunizations show that interleukin-2 (IL-2) and IL-4 are elicited by the three confirmed candidates, but unexpectedly interferon-γ and tumor necrosis factor-α are not. We suggest that these pathogen components, discovered using genetic immunization and confirmed in a conventional protein format, will be useful toward the development of a safe and effective glanders vaccine.
Insights
Researchers identified novel vaccine candidates against Burkholderia mallei, a dangerous bacterium. Three candidates provided partial protection in mice, offering hope for a new glanders vaccine.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- * Burkholderia species, particularly B. mallei and B. pseudomallei, are Gram-negative bacteria posing significant bioweapon and opportunistic infection risks.
- * These pathogens are difficult to treat with antibiotics and lack an existing vaccine, necessitating novel prevention strategies.
- * Increased incidence of infections in immunocompromised and diabetic populations heightens the urgency for effective medical countermeasures.
Purpose of the Study:
- * To identify potential protective antigens from the B. mallei genome for vaccine development.
- * To screen for gene-encoded protective antigens using a customized expression library immunization protocol.
- * To evaluate the efficacy of identified vaccine candidates in a preclinical animal model.
Main Methods:
- * Genomic-scale functional screening of the B. mallei ATCC23344 strain using expression library immunization.
- * Customization of the screening protocol to manage the complexity of Burkholderia.
- * Testing of five selected protein immunogens in a murine model of lethal pulmonary infection.
- * Analysis of peripheral blood cytokine and chemokine profiles post-immunization.
Main Results:
- * Identification of 12 new putative vaccine candidates against B. mallei.
- * Three of the five tested protein immunogens conferred significant partial protection against lethal pulmonary infection in mice.
- * Immunization with confirmed candidates elicited Interleukin-2 (IL-2) and Interleukin-4 (IL-4), but not Interferon-γ or Tumor Necrosis Factor-α.
Conclusions:
- * Novel vaccine candidates against B. mallei have been discovered through genomic screening and validated as protein immunogens.
- * The identified candidates demonstrate potential for developing a safe and effective vaccine against glanders.
- * Further research into these candidates could lead to a crucial medical countermeasure for B. mallei infections.
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