Layering vaccination with antibiotic therapy results in protection and clearance of Burkholderia pseudomallei in Balb/c mice

被引:0
|
作者
Barnes, Kay B. [1 ]
Brett, Paul [2 ,3 ]
Burtnick, Mary [2 ,3 ]
Vente, Andreas [4 ]
Bentley, Christine [4 ]
Richards, Mark I. [1 ]
Flick-Smith, Helen C. [1 ]
Burgess, Gary [1 ]
Thwaite, Joanne E. [1 ]
Laws, Thomas R. [1 ]
Maishman, Thomas C. [1 ]
Nelson, Michelle [1 ]
Harding, Sarah V. [1 ,5 ]
机构
[1] Def Sci & Technol Lab, Salisbury, England
[2] Univ Nevada, Reno Sch Med, Reno, NV USA
[3] Mahidol Univ, Bangkok, Thailand
[4] MerLion Pharmaceut, Berlin, Germany
[5] Univ Leicester, Leicester, England
关键词
melioidosis; finafloxacin; layered defence; subunit vaccine; Balb/c; Burkholderia pseudomallei; IMMUNE-RESPONSES; FINAFLOXACIN; FLUOROQUINOLONE; MELIOIDOSIS; PH; IDENTIFICATION;
D O I
10.1128/iai.00455-23
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Melioidosis is a disease that is difficult to treat due to the causative organism, Burkholderia pseudomallei being inherently antibiotic resistant and it having the ability to invade, survive, and replicate in an intracellular environment. Combination therapy approaches are routinely being evaluated in animal models with the aim of improving the level of protection and clearance of colonizing bacteria detected. In this study, a subunit vaccine layered with the antibiotic finafloxacin was evaluated in vivo against an inhalational infection with B. pseudomallei in Balb/c mice. Groups of mice vaccinated, infected, and euthanized at antibiotic initiation had a reduced bacterial load compared to those that had not been immunized. In addition, the subunit vaccine provided a synergistic effect when it was delivered with a CpG ODN and finafloxacin was initiated at 48 h post-challenge. Vaccination was also shown to improve the outcome, in a composite measure of survival and clearance. In summary, layering a subunit vaccine with the antibiotic finafloxacin is a promising therapeutic alternative for use in the treatment of B. pseudomallei infections.
引用
收藏
页数:14
相关论文
共 50 条
  • [1] Oropharyngeal Aspiration of Burkholderia mallei and Burkholderia pseudomallei in BALB/c Mice
    Schully, Kevin L.
    Bell, Matthew G.
    Ward, Jerrold M.
    Keane-Myers, Andrea M.
    PLOS ONE, 2014, 9 (12):
  • [2] Experimental acute respiratory Burkholderia pseudomallei infection in BALB/c mice
    Lever, Mark S.
    Nelson, Michelle
    Stagg, Anthony J.
    Beedham, Richard J.
    Simpson, Andrew J. H.
    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2009, 90 (01) : 16 - 25
  • [3] Burkholderia pseudomallei aerosol infection results in differential inflammatory responses in BALB/c and C57BI/6 mice
    Tan, Gek-Yen Gladys
    Liu, Yichun
    Sivalingam, Suppiah Paramalingal
    Sim, Siew-Hoon
    Wang, Dongling
    Paucod, Jean-Charles
    Gauthier, Yves
    Ooi, Eng-Eong
    JOURNAL OF MEDICAL MICROBIOLOGY, 2008, 57 (04) : 508 - 515
  • [4] An Investigation into the Re-Emergence of Disease Following Cessation of Antibiotic Treatment in Balb/c Mice Infected with Inhalational Burkholderia pseudomallei
    Laws, Thomas R.
    Barnes, Kay B.
    Jenner, Dominic C.
    Nunez, Alejandro
    Richards, Mark, I
    Thwaite, Joanne E.
    Vente, Andreas
    Rushton, David
    Nelson, Michelle
    Harding, Sarah, V
    ANTIBIOTICS-BASEL, 2022, 11 (10):
  • [5] Histopathological and immunohistochemical characterization of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice
    Garcia-Jimenez, Waldo Luis
    Salguero, Francisco J.
    D'Elia, Riccardo V.
    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2017, 98 (06) : 347 - 355
  • [6] Immunisation with tetanus toxin HC fragment exacerbates lethal Burkholderia pseudomallei infection in BALB/c mice
    Laws, T. R.
    Scott, A. E.
    Ngugi, S. A.
    Lonsdale, C. L.
    D'Elia, R. V.
    Williamson, E. D.
    Prior, J. L.
    Atkins, T. P.
    IMMUNOLOGY, 2013, 140 : 200 - 200
  • [7] Establishment of BALB/C Mice Model for the Acute and Chronic Forms of Human Melioidosis Caused by Burkholderia pseudomallei
    Samy, R. Perumal
    Gopalakrishnakone, P.
    Bow, H.
    Cow, V. T. K.
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2008, 12 : E172 - E172
  • [8] CpG-modified plasmid DNA encoding flagellin improves immunogenicity and provides protection against Burkholderia pseudomallei infection in BALB/c mice
    Chen, YS
    Hsiao, YS
    Lin, HH
    Liu, Y
    Chen, YL
    INFECTION AND IMMUNITY, 2006, 74 (03) : 1699 - 1705
  • [9] Immunogenicity and anti-Burkholderia pseudomallei activity in Balb/c mice immunized with plasmid DNA encoding flagellin
    Chen, YS
    Hsiao, YS
    Lin, HH
    Yen, CM
    Chen, SC
    Chen, YL
    VACCINE, 2006, 24 (06) : 750 - 758
  • [10] Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice
    Puangpetch, Apichaya
    Anderson, Robert
    Huang, Yan Y.
    Sermswan, Rasana W.
    Chaicumpa, Wanpen
    Sirisinha, Stitaya
    Wongratanacheewin, Surasakdi
    CLINICAL AND VACCINE IMMUNOLOGY, 2012, 19 (05) : 675 - 683