Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge
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PROVIDER: PRJNA953973 | ENA |
REPOSITORIES: ENA
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Project description:C57BL/6 mice were immunized with Coxiella burnetii vaccine Q-VAX (Seqirus) and monitored for up to 83 days post immunization. Two different routes of immunization were observed - subcutaneous and intramuscular. Subcutaneously immunized animals were boosted on day 67.
2023-04-11 | GSE229293 | GEO
Project description:Vaccines are among the most cost-effective public health measures for controlling infectious diseases. Coxiella burnetii is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX® contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the C. burnetii proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without C. burnetii lipopolysaccharide (LPS) in immunogenicity studies in vivo in mice and in a Hartley guinea pig intratracheal aerosol challenge model using C. burnetii strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. C. burnetii LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.
| S-EPMC10390735 | biostudies-literature
Project description:Transcriptional profiling of Coxiella burnetii phase I (RSA 493) submitting either to Cold and Heat shock comparing to control untreated Coxiella burnetii phase I (RSA 493) grown at 35°C.
2011-01-01 | GSE21778 | GEO
Project description:Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium usually found in myeloid cells. The infection is a source of severe obstetrical complications in humans and cattle, and of chronic evolution in pregnant women. As C. burnetii is found in the placenta of aborted foetuses in humans and ruminants, we wondered if it may infect trophoblasts. In this work, we showed that C. burnetii, infected JEG trophoblastic cells without replication and was localized within phagolysosomes. We analyzed gene expression programs induced by C. burnetii in JEG trophoblastic cell line and compared it with transcriptomic program of BeWo trophoblasts in which C. burnetii replicates. These transcriptomic programs induced by C. burnetii in JEG trophoblasts was poor and markedly different from that induced by C. burnetii in BeWo trophoblasts. Hence, the differences in transcriptomic programs may explain the different intracellular fate of C. burnetii in JEG and BeWo cells. Our results suggest that C. burnetii may use trophoblastic cells as a reservoir by interfering with gene expression.
2012-12-07 | GSE30330 | GEO
Project description:Coxiella burnetii, the etiological agent of Q fever, undergoes a unique biphasic developmental cycle where bacteria transition from replicating (exponential phase) large cell variant (LCV) forms to a non-replicating, (stationary phase) small cell variant (SCV) forms. The alternative sigma factor RpoS is an essential regulator of stress responses and stationary phase growth in several bacterial species, including Legionella pneumophila, which has a developmental cycle superficially similar to C. burnetii. To characterize RpoS function during C. burnetii growth and developmental, we constructed a C. burnetii ∆rpoS mutant to define the effects on intracellular and axenic growth, as well as, gene regulation during SCV development. C. burnetii ∆rpoS exhibited intracellular growth defects in J774 mouse macrophage-like cells, but not in Vero epithelial cells. RNA sequencing of C. burnetii ∆rpoS revealed that a substantial portion of the C. burnetii genome is regulated by RpoS during SCV development. Genes previously shown to have increased expression during SCV generation, including the expression of the SCV-specific protein ScvA and pathways involved in oxidative stress, arginine transport, and peptidoglycan remodeling pathways, were dysregulated in the rpoS mutant. These genes were enriched for a predicted RpoS-binding site. These data were corroborated with independent assays demonstrating that the C. burnetii rpoS mutant had increased sensitivity to hydrogen peroxide and carbenicillin. Collectively, these results demonstrate that RpoS is essential for the regulation of genes involved in SCV development and growth inside macrophage-like cells.
2019-02-08 | GSE110091 | GEO
Project description:Coxiella burnetii undergoes a biphasic developmental cycle within its host cell that generates morphologically and physiologically distinct large cell variants (LCV) and small cell variants (SCV). During the lag phase of the C. burnetii growth cycle, non-replicating SCV differentiate into replicating LCV that in turn differentiate back into SCV during stationary phase. Nearly homogeneous SCV are observed in infected Vero cells after extended incubation (21 to 28 days). In the current study, we sought to establish whether C. burnetii developmental transitions in host cells are recapitulated during host cell-free (axenic) growth in first and second generation acidified citrate cysteine media (ACCM-1 and ACCM-2, respectively). We show that ACCM-2 supported developmental transitions and viability. Although ACCM-1 also supported SCV to LCV transition, LCV to SCV transition did not occur after extended incubation (21 days). Instead, C. burnetii exhibited a ghost-like appearance with bacteria containing condensed chromatin but otherwise devoid of cytoplasmic content. This phenotype correlated with a near total loss in viability between 14 and 21 days of cultivation. Transcriptional profiling of C. burnetii following 14 days of incubation revealed elevated expression of oxidative stress genes in ACCM-1 cultivated bacteria. ACCM-2 differs from ACCM-1 by the substitution of methyl-b-cyclodextrin (Mb-CD) for fetal bovine serum. Addition of Mb-CD to ACCM-1 at 7 days post-inoculation rescued C. burnetii viability and lowered expression of oxidative stress genes. Thus, Mb-CD appears to alleviate oxidative stress in ACCM-2 to result in C. burnetii developmental transitions and viability that mimic host cell-cultivated organisms. Axenic cultivation of C. burnetii in ACCM-2 and new methods
2013-12-02 | GSE51135 | GEO
Project description:Genotyping based on genomic comparative hybridization of different isolates of coxiella burnetii compared to NMI reference strain
2011-12-31 | GSE31543 | GEO
Project description:Coxiella burnetii, the agent of Q fever, persists in humans despite specific immune responses: however, its reservoir remains unknown. We detected C. burnetii in adipose tissue from BALB/c and C57/BL6 mice 4 months after infection when no bacteria were found in other tissues. C. burnetii infected cultivated adipocytes, replicated within late phagosomes and induced a transcriptional program that was enriched for the expression of genes associated with inflammatory response, hormonal responses and cytoskeleton.
2014-05-25 | GSE46335 | GEO
Project description:The inability to propagate obligate intracellular pathogens under axenic (host cell-free) culture conditions imposes severe experimental constraints that have negatively impacted progress in understanding pathogen virulence and disease mechanisms. Coxiella burnetii, the causative agent of human Q (Query) fever, is an obligate intracellular bacterial pathogen that replicates exclusively in an acidified, lysosome-like vacuole. To define conditions that support C. burnetii growth, we systematically evaluated the organism’s metabolic requirements using expression microarrays, genomic reconstruction, and metabolite typing. This led to development of a complex nutrient medium that supported substantial growth (~ 3 log10) of C. burnetii in a 2.5% oxygen environment. Importantly, axenically grown C. burnetii were highly infectious for Vero cells and exhibited developmental forms characteristic of in vivo grown organisms. Axenic cultivation of C. burnetii will facilitate studies of the organism’s pathogenesis and genetics, and aid development of Q fever preventatives such as an effective subunit vaccine. Furthermore, the systematic approach used here may be broadly applicable to development of axenic media that support growth of other medically important obligate intracellular pathogens.
2009-10-21 | GSE13338 | GEO