Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1

Burkholderia pseudomallei is a facultative intracellular bacterium found in soil, which causes melioidosis, a disease with diverse symptomatology. B. pseudomallei is an emerging threat in the United States based on recent environmental samples and case reports. Acute infection is 10%–40% fatal depen...

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Main Authors: Michael L. Davies, Sergei S. Biryukov, Christopher P. Klimko, Jennifer L. Dankmeyer, Nathaniel O. Rill, Melissa Hunter, Christopher T. Braun, Deven W. Patrick, Tyrique D. David, Steven A. Kwilas, Carlos I. Rodriguez, Brian A. Smith, Ju Qiu, Jay W. Hooper, Christopher K. Cote
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Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612540/full
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author Michael L. Davies
Sergei S. Biryukov
Christopher P. Klimko
Jennifer L. Dankmeyer
Nathaniel O. Rill
Melissa Hunter
Christopher T. Braun
Deven W. Patrick
Tyrique D. David
Steven A. Kwilas
Carlos I. Rodriguez
Brian A. Smith
Ju Qiu
Jay W. Hooper
Christopher K. Cote
author_facet Michael L. Davies
Sergei S. Biryukov
Christopher P. Klimko
Jennifer L. Dankmeyer
Nathaniel O. Rill
Melissa Hunter
Christopher T. Braun
Deven W. Patrick
Tyrique D. David
Steven A. Kwilas
Carlos I. Rodriguez
Brian A. Smith
Ju Qiu
Jay W. Hooper
Christopher K. Cote
author_sort Michael L. Davies
collection DOAJ
description Burkholderia pseudomallei is a facultative intracellular bacterium found in soil, which causes melioidosis, a disease with diverse symptomatology. B. pseudomallei is an emerging threat in the United States based on recent environmental samples and case reports. Acute infection is 10%–40% fatal depending on treatment conditions. No vaccines for B. pseudomallei have been approved for human use, although several are under development, mostly targeting the antigens Hcp1 (hemolysin-coregulated protein 1) and CPS (capsular polysaccharide). For development of new vaccines, DNA compares favorably to other platforms in storage stability, low cost, and ease of design. Needle-free jet injection has been effective in immunizing against several infections in laboratory animals; the delivery devices are simple to use and have been FDA 510k cleared for human use. Herein, we developed a DNA vaccine targeting Hcp1 (pWRG/Hcp1) and delivered it to rabbits and mice by jet injection using a PharmaJet Stratis and a prototype adjustable-dose PharmaJet Tropis, respectively. The Hcp1 DNA vaccine was unadjuvanted and not combined with any other B. pseudomallei antigens. Immunization was followed by assessment of serum antibodies and cellular immunity against Hcp1 protein. Rabbits and mice showed induction of anti-Hcp1 antibodies after as few as two doses of pWRG/Hcp1, and splenocytes responsive to restimulation with Hcp1 protein were also detected after two doses. These results demonstrate the feasibility of inducing immunity against Hcp1 of B. pseudomallei using DNA alone. These results also serve as a proof-of-concept for immunizing mice with a PharmaJet device previously only used for larger animals.
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spelling doaj-art-dde386f4221e40b494eb7f4a77683bad2025-08-20T03:26:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.16125401612540Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1Michael L. Davies0Sergei S. Biryukov1Christopher P. Klimko2Jennifer L. Dankmeyer3Nathaniel O. Rill4Melissa Hunter5Christopher T. Braun6Deven W. Patrick7Tyrique D. David8Steven A. Kwilas9Carlos I. Rodriguez10Brian A. Smith11Ju Qiu12Jay W. Hooper13Christopher K. Cote14Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBiostatistics Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesVirology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United StatesBurkholderia pseudomallei is a facultative intracellular bacterium found in soil, which causes melioidosis, a disease with diverse symptomatology. B. pseudomallei is an emerging threat in the United States based on recent environmental samples and case reports. Acute infection is 10%–40% fatal depending on treatment conditions. No vaccines for B. pseudomallei have been approved for human use, although several are under development, mostly targeting the antigens Hcp1 (hemolysin-coregulated protein 1) and CPS (capsular polysaccharide). For development of new vaccines, DNA compares favorably to other platforms in storage stability, low cost, and ease of design. Needle-free jet injection has been effective in immunizing against several infections in laboratory animals; the delivery devices are simple to use and have been FDA 510k cleared for human use. Herein, we developed a DNA vaccine targeting Hcp1 (pWRG/Hcp1) and delivered it to rabbits and mice by jet injection using a PharmaJet Stratis and a prototype adjustable-dose PharmaJet Tropis, respectively. The Hcp1 DNA vaccine was unadjuvanted and not combined with any other B. pseudomallei antigens. Immunization was followed by assessment of serum antibodies and cellular immunity against Hcp1 protein. Rabbits and mice showed induction of anti-Hcp1 antibodies after as few as two doses of pWRG/Hcp1, and splenocytes responsive to restimulation with Hcp1 protein were also detected after two doses. These results demonstrate the feasibility of inducing immunity against Hcp1 of B. pseudomallei using DNA alone. These results also serve as a proof-of-concept for immunizing mice with a PharmaJet device previously only used for larger animals.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612540/fullmelioidosisBurkholderia pseudomalleivaccinesDNA vaccinesneedle-free injectionmice
spellingShingle Michael L. Davies
Sergei S. Biryukov
Christopher P. Klimko
Jennifer L. Dankmeyer
Nathaniel O. Rill
Melissa Hunter
Christopher T. Braun
Deven W. Patrick
Tyrique D. David
Steven A. Kwilas
Carlos I. Rodriguez
Brian A. Smith
Ju Qiu
Jay W. Hooper
Christopher K. Cote
Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1
Frontiers in Immunology
melioidosis
Burkholderia pseudomallei
vaccines
DNA vaccines
needle-free injection
mice
title Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1
title_full Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1
title_fullStr Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1
title_full_unstemmed Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1
title_short Immune responses following DNA vaccination by needle-free injection against Burkholderia pseudomallei hemolysin co-regulated protein 1
title_sort immune responses following dna vaccination by needle free injection against burkholderia pseudomallei hemolysin co regulated protein 1
topic melioidosis
Burkholderia pseudomallei
vaccines
DNA vaccines
needle-free injection
mice
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1612540/full
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