Distinct human antibody response to the biological warfare agent<i>Burkholderia mallei</i>

Varga, John J.; Vigil, Adam; DeShazer, David; Waag, David M.; Felgner, Philip L.; Goldberg, Joanna B.

doi:10.4161/viru.22056

Cited by 19 publications

(19 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The T helper cells contribute the class switch and affinity maturation for stronger immunoreactivity. Other researchers have reported similar results of elevated IgG and IgM post infection with B. mallei , a closely related species to B. pseudomallei [48].…”

Section: Discussionsupporting

confidence: 56%

Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

Simpanya

Settles

et al. 2018

Preprint

View full text Add to dashboard Cite

29Burkholderia pseudomallei causes melioidosis, a common source of pneumonia and sepsis in 30 Southeast Asia and Northern Australia, that results in high mortality rates. A caprine melioidosis 31 model of aerosol infection that leads to a systemic infection has the potential to characterize the 32 humoral immune response. This could help identify immunogenic proteins for new diagnostics 33 and vaccine candidates. Outbred goats may more accurately mimic human infection, in contrast to 34 the inbred mouse models used to date. B. pseudomallei infection was delivered as an intratracheal 35 aerosol. Antigenic protein profiling was generated from the infecting strain MSHR511. Humoral 36 immune responses were analyzed by ELISA and western blot, and the antigenic proteins were 37 identified by mass spectrometry. Throughout the course of the infection the assay results 38 demonstrated a much greater humoral response with IgG antibodies, in both breadth and quantity, 39 compared to IgM antibodies. Pre-infection sera showed multiple immunogenic proteins already 40 reactive for IgG (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and IgM (0-12) in most of the goats despite no previous exposure to B. 41 pseudomallei. After infection, the number of IgG reactive proteins showed a marked increase as 42 the disease progressed. Early stage infection (day 7) showed immune reaction to chaperone 43 proteins (GroEL, EF-Tu, and DnaK). These three proteins were detected in all serum samples after 3 44 infection, with GroEL immunogenically dominant. Seven common reactive antigens were selected 45 for further analysis using ELISA. The heat shock protein GroEL1 elicited the strongest goat 46 antibody immune response compared to the other six antigens. Most of the six antigens showed 47 the peak IgM reactivity at day 14, whereas the IgG reactivity increased further as the disease 48 progressed. An overall MSHR511 proteomic comparison between the goat model and human sera 49 showed that many immune reactive proteins are common between humans and goats with 50 melioidosis. 51 52 Author Summary 53 B. pseudomallei infection, the causative agent of melioidosis, results in severe 54 disseminated or localized infections. A systemic study of the humoral immune response to B. 55 pseudomallei infection using the B. pseudomallei aerosol caprine model would help understand 56 the detectable antigenic proteins as the infection progresses. To study the immune response, IgG 57 and IgM antibody responses to whole cell lysate proteins were identified and analyzed. Antigenic 58 carbohydrates were also studied. From the results, this study suggests that the caprine humoral 59 immune response to aerosolized B. pseudomallei has similarities to human melioidosis and may 60 facilitate the analysis of the temporal antibody responses. In addition, commonly detected 61 immunogenic proteins may be used as biomarkers for the future point of care (POC) diagnostics.62 4 63 Introduction 64 Burkholderia pseudomallei is a Gram-negative, non-spore formin...

show abstract

Section: Discussionsupporting

confidence: 56%

Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

Simpanya

Settles

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…mallei and are arguably the most relevant surrogate to study glanders. Using protein microarray technology, Varga et al demonstrated that serum from a human patient with glanders also contain increased levels of α-BpaB antibodies [ 70 ]. Our animal experiments showing that a mutation in bpaB attenuates virulence (Figs 5 and 7 , S1 Fig ) substantiate these observations and underscore the potential usefulness of BpaB as a target for developing countermeasures.…”

Section: Discussionmentioning

confidence: 99%

The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in an Aerosol Model of Infection

et al. 2015

View full text Add to dashboard Cite

Burkholderia mallei is a highly pathogenic bacterium that causes the zoonosis glanders. Previous studies indicated that the genome of the organism contains eight genes specifying autotransporter proteins, which are important virulence factors of Gram-negative bacteria. In the present study, we report the characterization of one of these autotransporters, BpaB. Database searches identified the bpaB gene in ten B. mallei isolates and the predicted proteins were 99-100% identical. Comparative sequence analyses indicate that the gene product is a trimeric autotransporter of 1,090 amino acids with a predicted molecular weight of 105-kDa. Consistent with this finding, we discovered that recombinant bacteria expressing bpaB produce a protein of ≥300-kDa on their surface that is reactive with a BpaB-specific monoclonal antibody. Analysis of sera from mice infected with B. mallei indicated that animals produce antibodies against BpaB during the course of disease, thus establishing production of the autotransporter in vivo. To gain insight on its role in virulence, we inactivated the bpaB gene of B. mallei strain ATCC 23344 and determined the median lethal dose of the mutant in a mouse model of aerosol infection. These experiments revealed that the bpaB mutation attenuates virulence 8-14 fold. Using a crystal violet-based assay, we also discovered that constitutive production of BpaB on the surface of B. mallei promotes biofilm formation. To our knowledge, this is the first report of a biofilm factor for this organism.

show abstract

“…pseudomallei protein array platform and comparing sera from healthy control subjects form South East Asia, patients either recovered from or with acute melioidosis [ 90 , 91 ], and a laboratory worker accidentally infected with B . mallei [ 92 ]. A number of proteins were recognized by antibodies from melioidosis and glanders but not control patients.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders

et al. 2015

Self Cite

View full text Add to dashboard Cite

Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

show abstract

Distinct human antibody response to the biological warfare agentBurkholderia mallei

Cited by 19 publications

References 19 publications

Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in an Aerosol Model of Infection

Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders

Contact Info

Product

Resources

About