Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei
| Autor: | Mridul Kalita, Laura A. Muruato, Richard W. Titball, Paul J. Brett, Alfredo G. Torres, Anthony E. Gregory, Daniel Tapia, James E. Samuel, Christopher L. Hatcher |
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| Rok vydání: | 2017 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine Microbiology (medical) Burkholderia pseudomallei Melioidosis Clinical Biochemistry Immunology Metal Nanoparticles Major histocompatibility complex Mice 03 medical and health sciences Antigen medicine Animals Humans Immunology and Allergy Antigens Bacterial Vaccines biology Immunogenicity Reverse vaccinology Respiratory infection biology.organism_classification medicine.disease Antibodies Bacterial Virology Mice Inbred C57BL Vaccinology 030104 developmental biology Burkholderia Bacterial Vaccines Models Animal biology.protein Female Gold Glycoconjugates |
| Zdroj: | Clinical and Vaccine Immunology. 24 |
| ISSN: | 1556-679X 1556-6811 |
| Popis: | Burkholderia pseudomallei is a Gram-negative, facultative intracellular pathogen that causes the disease melioidosis in humans and other mammals. Respiratory infection with B. pseudomallei leads to a fulminant and often fatal disease. It has previously been shown that glycoconjugate vaccines can provide significant protection against lethal challenge; however, the limited number of known Burkholderia antigens has slowed progress toward vaccine development. The objective of this study was to identify novel antigens and evaluate their protective capacity when incorporated into a nanoglycoconjugate vaccine platform. First, an in silico approach to identify antigens with strong predicted immunogenicity was developed. Protein candidates were screened and ranked according to predicted subcellular localization, transmembrane domains, adhesive properties, and ability to interact with major histocompatibility complex (MHC) class I and class II. From these in silico predictions, we identified seven “high priority” proteins that demonstrated seroreactivity with anti- B. pseudomallei murine sera and convalescent human melioidosis sera, providing validation of our methods. Two novel proteins, together with Hcp1, were linked to lipopolysaccharide (LPS) and incorporated with the surface of a gold nanoparticle (AuNP). Animals receiving AuNP glycoconjugate vaccines generated high protein- and polysaccharide-specific antibody titers. Importantly, immunized animals receiving the AuNP-FlgL-LPS alone or as a combination demonstrated up to 100% survival and reduced lung colonization following a lethal challenge with B. pseudomallei . Together, this study provides a rational approach to vaccine design that can be adapted for other complex pathogens and provides a rationale for further preclinical testing of AuNP glycoconjugate in animal models of infection. |
| Databáze: | OpenAIRE |
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