Infection with Burkholderia pseudomallei – immune correlates of survival in acute melioidosis

Dunachie, Susanna; Jenjaroen, Kemajittra; Reynolds, Catherine J.; Quigley, Kathryn; Sergeant, Ruhena; Sumonwiriya, Manutsanun; Chaichana, Panjaporn; Chumseng, Suchintana; Ariyaprasert, Pitchayanant; Lassaux, Patricia; Gourlay, L.J.; Promwong, Charuporn; Teparrukkul, Prapit; Limmathurotsakul, Direk; Day, Nicholas P. J.; Altmann, Daniel M.; Boyton, Rosemary J.

doi:10.1038/s41598-017-12331-5

Cited by 40 publications

(71 citation statements)

References 46 publications

(56 reference statements)

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“…Although there was no difference in HbA1c levels based on outcome, the acute melioidosis group with DM showed significantly worse glycemic control compared to the endemic control group, as reported previously . Melioidosis patients without DM were comprised of a heterogeneous population of individuals with one or more risk factors other than diabetes . Renal failure was highly associated with death in this patient group.…”

Section: Resultssupporting

confidence: 68%

Diabetes alters immune response patterns to acute melioidosis in humans

et al. 2019

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Diabetes mellitus (DM) is a serious global health problem currently affecting over 450 million people worldwide. Defining its interaction with major global infections is an international public health priority. Melioidosis is caused by Burkholderia pseudomallei, an exemplar pathogen for studying intracellular bacterial infection in the context of DM due to the 12‐fold increased risk in this group. We characterized immune correlates of survival in peripheral blood of acute melioidosis patients with and without DM and highlight different immune response patterns. We demonstrate the importance of circulating NK cells and show that CX3CR1 expression on lymphocytes is a novel correlate of survival from acute melioidosis. Furthermore, excessive serum levels of IL‐15 and IL‐18BP contribute to poor outcome independent of DM comorbidity. CD8+ T cells and granzyme B expression in NK cells are important for survival of non‐DM patients, whereas high antibody titers against B. pseudomallei and double‐negative T cells are linked to survival of DM patients. Recall responses support a role of γδ T‐cell‐derived IFN‐γ in the establishment of protective immunity in the DM group. Defining the hallmarks of protection in people with DM is crucial for the design of new therapies and vaccines targeting this rapidly expanding risk group.

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Section: Resultssupporting

confidence: 68%

Diabetes alters immune response patterns to acute melioidosis in humans

et al. 2019

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“…However, commonly detected immunogenic proteins with the different timelines for antibody characterization generate the antibody response to the same or similar epitopes despite the host variability to infection. These common immunogenic proteins are mainly immunodominant proteins (S4 Table) [49]. These common immunogenic proteins give the insight of how the host generally reacts to the infection and it also demonstrates those proteins’ potential as general diagnostic antigens for bacterial infection.…”

Section: Discussionmentioning

confidence: 99%

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

Simpanya

Settles

et al. 2018

Preprint

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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...

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“…PART 1 from human melioidosis patients as well as animal studies has greatly facilitated the selection of target antigens and rational design of candidate vaccines [33][34][35][36][37][38][39][40][41][42][43]. The identification of immunoreactive B and T cell antigens VACCINES FOR EMERGING PATHOGENS: FROM RESEARCH TO THE CLINIC.…”

Section: Multi-component Vaccinesmentioning

confidence: 99%

“…The identification of immunoreactive B and T cell antigens VACCINES FOR EMERGING PATHOGENS: FROM RESEARCH TO THE CLINIC. PART 1 from human melioidosis patients as well as animal studies has greatly facilitated the selection of target antigens and rational design of candidate vaccines [33][34][35][36][37][38][39][40][41][42][43]. Certain bacterial antigens, such as capsule polysaccharide (CPS), FliC, BopE, AhpC and many outer membrane proteins (Omp), are routinely recognized as highly reactive with patient immune sera or peripheral blood mononuclear cells (PBMCs), and many of these antigens confer partial protection when used as individual subunit vaccines [7].…”

Section: Multi-component Vaccinesmentioning

confidence: 99%

Novel multi-component vaccine approaches for Burkholderia pseudomallei

Morici

Torres

Titball

2019

Clinical and Experimental Immunology

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Burkholderia pseudomallei is the causative agent of melioidosis. Historically believed to be a relatively rare human disease in tropical countries, a recent study estimated that, worldwide, there are approximately 165 000 human melioidosis cases per year, more than half of whom die. The bacterium is inherently resistant to many antibiotics and treatment of the disease is often protracted and ineffective. There is no licensed vaccine against melioidosis, but a vaccine is predicted to be of value if used in high-risk populations. There has been progress over the last decade in the pursuit of an effective vaccine against melioidosis. Animal models of disease including mouse and non-human primates have been developed, and these models show that antibody responses play a key role in protection against melioidosis. Surprisingly, although B. pseudomallei is an intracellular pathogen there is limited evidence that CD8 + T cells play a role in protection. It is evident that a multi-component vaccine, incorporating one or more protective antigens, will probably be essential for protection because of the pathogen's sophisticated virulence mechanisms as well as strain heterogeneity. Multi-component vaccines in development include glycoconjugates, multivalent subunit preparations, outer membrane vesicles and other nano/microparticle platforms and live-attenuated or inactivated bacteria. A consistent finding with vaccine candidates tested in mice is the ability to induce sterilizing immunity at low challenge doses and extended time to death at higher challenge doses. Further research to identify ways of eliciting more potent immune responses might provide a path for licensing an effective vaccine.

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Infection with Burkholderia pseudomallei – immune correlates of survival in acute melioidosis

Cited by 40 publications

References 46 publications

Diabetes alters immune response patterns to acute melioidosis in humans

Diabetes alters immune response patterns to acute melioidosis in humans

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

Novel multi-component vaccine approaches for Burkholderia pseudomallei

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