Immunization Experiments with Recombinant <i>Coxiella burnetii</i> Proteins in a Murine Infection Model

Tyczka, Judith; Eberling, Sandra; Baljer, G.

doi:10.1196/annals.1355.022

Cited by 13 publications

(5 citation statements)

References 14 publications

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“…The authors advised more blinded, randomized, and unbiased research on Qvax effectiveness. Development of recombinant protein subunit vaccines has proven disappointing [76, 288–290]. Before initiating a vaccination program, epidemiological knowledge of the area is necessary.…”

Section: Control Methods and Vaccinationmentioning

confidence: 99%

Q Fever: Current State of Knowledge and Perspectives of Research of a Neglected Zoonosis

Porter

Czaplicki²,

Mainil

et al. 2011

International Journal of Microbiology

182

201

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Q fever is an ubiquitous zoonosis caused by an resistant intracellular bacterium, Coxiella burnetii. In certain areas, Q fever can be a severe public health problem, and awareness of the disease must be promoted worldwide. Nevertheless, knowledge of Coxiella burnetii remains limited to this day. Its resistant (intracellular and environmental) and infectious properties have been poorly investigated. Further understanding of the interactions between the infected host and the bacteria is necessary. Domestic ruminants are considered as the main reservoir of bacteria. Infected animals shed highly infectious organisms in milk, feces, urine, vaginal mucus, and, very importantly, birth products. Inhalation is the main route of infection. Frequently asymptomatic in humans and animals, Q fever can cause acute or chronic infections. Financial consequences of infection can be dramatic at herd level. Vaccination with inactive whole-cell bacteria has been performed and proved effective in humans and animals. However, inactive whole-cell vaccines present several defects. Recombinant vaccines have been developed in experimental conditions and have great potential for the future. Q fever is a challenging disease for scientists as significant further investigations are necessary. Great research opportunities are available to reach a better understanding and thus a better prevention and control of the infection.

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Section: Control Methods and Vaccinationmentioning

confidence: 99%

Q Fever: Current State of Knowledge and Perspectives of Research of a Neglected Zoonosis

Porter

Czaplicki²,

Mainil

et al. 2011

International Journal of Microbiology

182

201

View full text Add to dashboard Cite

show abstract

“…By utilizing the axenic culture system, we removed the possibility of contamination by host-derived components. In line with previous results utilizing formalin-inactivated whole-cell vaccines derived from chicken eggs or tissue culture (117,119,146,203), axenically-generated PIV was able to prevent clinical disease in BALB/c mice.…”

Section: Discussionsupporting

confidence: 87%

“…CD4+ T cells are potent producers of IL-5, which promotes eosinophil differentiation, maturation, migration, and activation (202,203). Therefore, to determine if eosinophil accumulation in PIV-vaccinated spleens is dependent on signals from CD4+ T cells, we vaccinated CD4 KO mice with 10 µg PIV and assessed eosinophil numbers 7 days later.…”

Section: Eosinophil Accumulation In Piv-vaccinated Mice Is Cd4 + T Cell-dependentmentioning

confidence: 99%

Vaccine-induced protective immunity against coxiella burnetii

Ledbetter¹

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Coxiella burnetii is an obligate intracellular Gram-negative bacterial pathogen and the causative agent of human Q fever. This disease presents acutely as a flu-like illness, although it can escalate to a chronic and often fatal disease when left untreated. Considering no FDA-approved vaccine exists, the creation of a safe and effective vaccine remains an important public health goal. A formalin-inactivated C. burnetii Nine Mile strain phase I whole-cell vaccine generates protective immunity in a mouse model of experimental Q fever, although the mechanisms of protection remain unclear. Chapter 3 details my work establishing an early vaccine protection model and elucidating the cellular immune response which elicits early protection. The early time point at which PIV protects has implications for its use as a therapeutic vaccine. Furthermore, the innate-driven mechanisms by which it protects can be exploited for an improved Q fever vaccine. The importance of T cells in vaccine immunity against C. burnetii is well supported, however, multiple questions remain. It is unclear how CD4+ or CD8+ T cells contribute to vaccine protection, and the role of specific CD4+ T cell subsets is unknown. IFN-[theta] is critical for primary defense against C. burnetii, though its importance in vaccine immunity is undetermined. Chapter 4 describes my work aimed at filling these knowledge gaps. Vaccine development efforts have largely focused on the generation of antibodies as a correlate of protection. It has become clear that targeting T cells is more critical to vaccine protection and a better understanding of the mechanisms of cell-mediated immunity will inform future Q fever vaccine development.

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“…(A) SSC high CD11b ϩ CD125 ϩ Siglec-F ϩ eosinophils were enumerated using the gating strategy described in the legends for Fig. 4 chicken eggs or tissue culture (25,32,52,53), axenically generated PIV was able to prevent clinical disease in BALB/c mice. There was a significant reduction in splenomegaly and an approximately 2-log decrease in C. burnetii genomic equivalents.…”

Section: Discussionmentioning

confidence: 99%

Eosinophils Affect Antibody Isotype Switching and May Partially Contribute to Early Vaccine-Induced Immunity against Coxiella burnetii

et al. 2019

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Coxiella burnetii is an obligate intracellular Gram-negative bacterium which causes human Q fever. An acidified citrate cysteine medium (ACCM-2) has been developed which mimics the intracellular replicative niche of C. burnetii and allows axenic growth of the bacteria. To determine if C. burnetii cultured in ACCM-2 retains immunogenicity, we compared the protective efficacies of formalin-inactivated C. burnetii Nine Mile phase I (PIV) and phase II (PIIV) vaccines derived from axenic culture 7, 14, and 28 days postvaccination. PIV conferred significant protection against virulent C. burnetii as early as 7 days postvaccination, which suggests that ACCM-2-derived PIV retains immunogenicity and protectivity. We analyzed the cellular immune response in spleens from PIV- and PIIV-vaccinated mice by flow cytometry at 7 and 14 days postvaccination and found significantly more granulocytes in PIV-vaccinated mice than in PIIV-vaccinated mice. Interestingly, we found these infiltrating granulocytes to be SSChigh CD11b+ CD125+ Siglec-F+ (where SSChigh indicates a high side scatter phenotype) eosinophils. There was no change in the number of eosinophils in PIV-vaccinated CD4-deficient mice compared to the level in controls, which suggests that eosinophil accumulation is CD4+ T cell dependent. To evaluate the importance of eosinophils in PIV-mediated protection, we vaccinated and challenged eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice had significantly worse disease than their wild-type counterparts when challenged 7 days postvaccination, while no significant difference was seen at 28 days postvaccination. Nevertheless, ΔdblGATA mice had elevated serum IgM with decreased IgG1 and IgG2a whether mice were challenged at 7 or 28 days postvaccination. These results suggest that eosinophils may play a role in early vaccine protection against C. burnetii and contribute to antibody isotype switching.

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Immunization Experiments with Recombinant Coxiella burnetii Proteins in a Murine Infection Model

Cited by 13 publications

References 14 publications

Q Fever: Current State of Knowledge and Perspectives of Research of a Neglected Zoonosis

Q Fever: Current State of Knowledge and Perspectives of Research of a Neglected Zoonosis

Vaccine-induced protective immunity against coxiella burnetii

Eosinophils Affect Antibody Isotype Switching and May Partially Contribute to Early Vaccine-Induced Immunity against Coxiella burnetii

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