Evaluating<i>Burkholderia pseudomallei</i>Bip proteins as vaccines and Bip antibodies as detection agents

Druar, Chris; Yu, Fei; Barnes, Jodie L.; Okinaka, Richard T.; Chantratita, Narisara; Beg, Steve; Stratilo, Chad W.; Olive, Andrew J.; Soltes, Glenn; Russell, Mary Jo; Limmathurotsakul, Direk; Norton, Robert; Ni, Sally X.; Picking, William D.; Jackson, Paul J.; Stewart, Don; Tsvetnitsky, Vadim; Picking, Wendy L.; Cherwonogrodzky, John W.; Ketheesan, Natkunam; Peacock, Sharon J.; Wiersma, Erik J.

doi:10.1111/j.1574-695x.2007.00345.x

Cited by 51 publications

(53 citation statements)

References 41 publications

(46 reference statements)

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“…Subunit vaccines have also been developed for immunization against B. pseudomallei, with the most promising protection to date being achieved with purified proteins such as BipD (34) and BipB and BipC (36); with recombinant proteins, including Hcp1, Hcp2, Hcp3, and Hcp6 (37); with lipopolysaccharide (LPS) (38); with purified flagellin (39); with LolC, PotF, and OppA nonmembrane protein (40); with outer membrane vesicles (41); and with recombinant Omp85 protein (42). However, the use of single antigen subunit vaccines for Burkholderia infection is unlikely to generate broad protective immunity against this very genetically diverse and unstable organism (35,43).…”

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confidence: 99%

Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

et al. 2013

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Infections with the Gram-negative bacterium Burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with B. pseudomallei. At present, our understanding of what constitutes effective protective immunity against B. pseudomallei infection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acute B. pseudomallei infection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excluded purM deletion mutant of B. pseudomallei (strain Bp82) and then subjected to intranasal challenge with virulent B. pseudomallei strain 1026b. Immunization with Bp82 generated significant protection from challenge with B. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccineinduced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuated Burkholderia vaccine strain was dependent primarily on generation of effective humoral immune responses.

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confidence: 99%

Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

et al. 2013

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“…In addition, CD4 ϩ T cells of some responders from the seropositive group could produce IFN-␥ at levels above the mean in response to the other proteins tested, including ABC (11,27). Conversely, recombinant flagellin could provide limited protection in mice, albeit not as great as that when the protein was given as a plasmid DNA vaccine or with specific adjuvants such as CpG (5,6,30).…”

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confidence: 99%

“…B. pseudomallei 2D2-primed T cells also recognize bacterial proteins of the ATPbinding cassette (ABC) family, including LolC, PotF, and OppA, and respond by producing IFN-␥ (18). In an assay to evaluate candidate vaccine antigens, immunization of mice with adjuvant-mixed Bip proteins did not elicit protection against B. pseudomallei infection (11,27). However, antibodies to BipB, BipC, and BipD have been detected in sera of melioidosis patients (11,28).…”

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confidence: 99%

“…In an assay to evaluate candidate vaccine antigens, immunization of mice with adjuvant-mixed Bip proteins did not elicit protection against B. pseudomallei infection (11,27). However, antibodies to BipB, BipC, and BipD have been detected in sera of melioidosis patients (11,28). Furthermore, a DNA vaccine encoding the flagellin protein and carrying CpG motifs enhanced resistance of immunized mice to B. pseudomallei (5,6).…”

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Burkholderia pseudomalleiProteins Presented by Monocyte-Derived Dendritic Cells Stimulate Human Memory T CellsIn Vitro

et al. 2011

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Melioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogen Burkholderia pseudomallei. The disease is endemic in Southeast Asia and Northern Australia, and no effective vaccine exists. To describe human cell-mediated immune responses to B. pseudomallei and to identify candidate antigens for vaccine development, the ability of antigen-pulsed monocyte-derived dendritic cells (moDCs) to trigger autologous T-cell responses to B. pseudomallei and its products was tested. moDCs were prepared from healthy individuals exposed or not exposed to B. pseudomallei, based on serological evidence. These were pulsed with heat-killed B. pseudomallei or purified antigens, including ABC transporters (LolC, OppA, and PotF), Bsa type III secreted proteins (BipD and BopE), tandem repeat sequence-containing proteins (Rp1 and Rp2), flagellin, and heat shock proteins (Hsp60 and Hsp70), prior to being mixed with autologous T-cell populations. After pulsing of cells with either heat-killed B. pseudomallei, LolC, or Rp2, coculturing the antigen-pulsed moDCs with T cells elicited gamma interferon production from CD4 ؉ T cells from seropositive donors at levels greater than those for seronegative donors. These antigens also induced granzyme B (cytotoxic) responses from CD8 ؉ T cells. Activation of antigen-specific CD4 ؉ T cells required direct contact with moDCs and was therefore not dependent on soluble mediators. Rp peptide epitopes recognized by T cells in healthy individuals were identified. Our study provides valuable novel data on the induction of human cell-mediated immune responses to B. pseudomallei and its protein antigens that may be exploited in the rational development of vaccines to combat melioidosis.

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“…Several antigens have been used for immunization against experimental B. pseudomallei infection in mice, including lipopolysaccharide (LPS), capsule polysaccharide, flagella (6,36,37), and several other bacterial proteins, including the lipoprotein releasing system transmembrane protein (LolC), an ATP-binding cassette transporter protein (20), and the type III secretion system protein (11). More recently, two outer membrane proteins (OmpAs) of B. pseudomallei that reacted with melioidosis patients' convalescent-phase sera have been identified: BPSL2522 (Omp3) and BPSL2765 (Omp7) (19).…”

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confidence: 99%

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice

Puangpetch¹,

Anderson²,

Huang³

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTMelioidosis is a severe disease caused by the Gram-negative bacteriumBurkholderia pseudomallei. Previously we showed that pretreatment of mice with CpG oligodeoxynucleotide (CpG ODN) 2 to 10 days prior toB. pseudomalleichallenge conferred as high as 90% protection, but this window of protection was rather short. In the present study, we therefore aimed to prolong this protective window and to gain further insight into the mechanisms underlying the protection induced by CpG ODN againstB. pseudomalleiinfection. It was found that the CpG ODN incorporated with cationic liposomes (DOTAP) but not zwitterionic liposomes (DOPC) provided complete protection against bacterial challenge. Although marked elevation of gamma interferon (IFN-γ) was found in the infected animals 2 days postinfection, it was significantly lowered by the DOTAP-plus-CpG ODN pretreatment. When appropriately activated, the phagocytic index and oxidative burst responses of neutrophils appeared not to be elevated. However, macrophages from stimulated mice showed higher levels of nitric oxide production and exhibited higher levels of antimicrobial activities, judging from lower numbers of viable intracellular bacteria. Taken together, our results demonstrate that DOTAP can enhance the protective window period of CpG ODN to at least 30 days and provide 100% protection againstB. pseudomalleiinfection. The protective effect of DOTAP plus CpG ODN could provide an alternative approach to preventing this lethal infection, for which no vaccine is yet available.

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EvaluatingBurkholderia pseudomalleiBip proteins as vaccines and Bip antibodies as detection agents

Cited by 51 publications

References 41 publications

Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

Burkholderia pseudomalleiProteins Presented by Monocyte-Derived Dendritic Cells Stimulate Human Memory T CellsIn Vitro

Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice

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