Characterization of a phase I Coxiella burnetii chloroform-methanol residue vaccine that induces active immunity against Q fever in C57BL/10 ScN mice.

ABSTRACT Although the phase I Coxiella burnetii cellular vaccine is completely efficacious in humans, adverse local and systemic reactions may develop if immune individuals are inadvertently vaccinated. The phase I chloroform-methanol residue (CMRI) vaccine was developed as a potentially safer alternative. Human volunteers with no evidence of previous exposure to C. burnetii received a subcutaneous vaccination with the CMRI vaccine in phase I studies under protocol IND 3516 to evaluate the safety and immunogenicity of the vaccine. This clinical trial tested escalating doses of the CMRI vaccine, ranging from 0.3 to 60 μg, followed by a booster dose of 30 μg, in a placebo-controlled study. Although priming doses of the CMRI vaccine did not induce a specific antibody detectable by enzyme-linked immunosorbent assay, booster vaccination stimulated the production of significant levels of anti-C. burnetii antibody. Peripheral blood cells (PBCs) of vaccinees responded to C. burnetii cellular antigen in vitro in a vaccine dose-dependent manner. After the booster dose, PBCs were activated by recall antigen in vitro, regardless of the priming dose. These findings suggest that vaccination with the CMRI vaccine can effectively prime the immune system to mount significant anamnestic responses after infection.

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Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity

npj Vaccines ◽

10.1038/s41541-021-00296-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Carrie M. Long ◽

Paul A. Beare ◽

Diane C. Cockrell ◽

Jonathan Fintzi ◽

Mahelat Tesfamariam ◽

...

Keyword(s):

Phase I ◽

Coxiella Burnetii ◽

Vaccine Efficacy ◽

Q Fever ◽

Secretion System ◽

Cell Vaccine ◽

Post Vaccination ◽

Whole Cell Vaccine ◽

Type Ivb Secretion ◽

Type Ivb Secretion System

AbstractCoxiella burnetii is the bacterial causative agent of the zoonosis Q fever. The current human Q fever vaccine, Q-VAX®, is a fixed, whole cell vaccine (WCV) licensed solely for use in Australia. C. burnetii WCV administration is associated with a dermal hypersensitivity reaction in people with pre-existing immunity to C. burnetii, limiting wider use. Consequently, a less reactogenic vaccine is needed. Here, we investigated contributions of the C. burnetii Dot/Icm type IVB secretion system (T4BSS) and lipopolysaccharide (LPS) in protection and reactogenicity of fixed WCVs. A 32.5 kb region containing 23 dot/icm genes was deleted in the virulent Nine Mile phase I (NMI) strain and the resulting mutant was evaluated in guinea pig models of C. burnetii infection, vaccination-challenge, and post-vaccination hypersensitivity. The NMI ∆dot/icm strain was avirulent, protective as a WCV against a robust C. burnetii challenge, and displayed potentially altered reactogenicity compared to NMI. Nine Mile phase II (NMII) strains of C. burnetii that produce rough LPS, were similarly tested. NMI was significantly more protective than NMII as a WCV; however, both vaccines exhibited similar reactogenicity. Collectively, our results indicate that, like phase I LPS, the T4BSS is required for full virulence by C. burnetii. Conversely, unlike phase I LPS, the T4BSS is not required for vaccine-induced protection. LPS length does not appear to contribute to reactogenicity while the T4BSS may contribute to this response. NMI ∆dot/icm represents an avirulent phase I strain with full vaccine efficacy, illustrating the potential of genetically modified C. burnetii as improved WCVs.

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Isolation and characterization of a plasmid from phase I Coxiella burnetii.

Infection and Immunity ◽

10.1128/iai.41.2.488-493.1983 ◽

1983 ◽

Vol 41 (2) ◽

pp. 488-493 ◽

Cited By ~ 41

Author(s):

J E Samuel ◽

M E Frazier ◽

M L Kahn ◽

L S Thomashow ◽

L P Mallavia

Keyword(s):

Phase I ◽

Coxiella Burnetii ◽

Isolation And Characterization

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Serological characterization of surface-exposed proteins of Coxiella burnetii

Microbiology ◽

10.1099/mic.0.082131-0 ◽

2014 ◽

Vol 160 (12) ◽

pp. 2718-2731 ◽

Cited By ~ 7

Author(s):

Jun Jiao ◽

Xiaolu Xiong ◽

Yong Qi ◽

Wenping Gong ◽

Changsong Duan ◽

...

Keyword(s):

Coxiella Burnetii ◽

Bioinformatics Analysis ◽

Q Fever ◽

Obligate Intracellular ◽

Rickettsia Rickettsii ◽

Serological Characterization ◽

Vaccine Antigens ◽

Mycoplasma Pneumonia ◽

Dimensional Electrophoresis

The obligate intracellular Gram-negative bacterium Coxiella burnetii causes Q fever, a worldwide zoonosis. Here we labelled Cox . burnetii with biotin and used biotin-streptavidin affinity chromatography to isolate surface-exposed proteins (SEPs). Using two-dimensional electrophoresis combined with mass spectrometry, we identified 37 proteins through bioinformatics analysis. Thirty SEPs expressed in Escherichia coli (recombinant SEPs, rSEPs) were used to generate microarrays, which were probed with sera from mice experimentally infected with Cox. burnetii or sera from Q fever patients. Thirteen rSEPs were recognized as seroreactive, and the majority reacted with at least 50 % of the sera from mice infected with Cox. burnetii but not with sera from mice infected with Rickettsia rickettsii, R. heilongjiangensis, or R. typhi. Further, 13 proteins that reacted with sera from patients with Q fever did not react with sera from patients with brucellosis or mycoplasma pneumonia. Our results suggest that these seroreactive SEPs have potential as serodiagnostic antigens or as subunit vaccine antigens against Q fever.

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Animals withCoxiella burnetiiInfection Demonstrate a Western Immunoblot Profile of Chronic Q Fever in Humans

Canadian Journal of Infectious Diseases ◽

10.1155/1996/853518 ◽

1996 ◽

Vol 7 (1) ◽

pp. 45-48

Author(s):

TJ Marrie ◽

Linda Yates

Keyword(s):

Immune Response ◽

Phase I ◽

Phase Ii ◽

Coxiella Burnetii ◽

Q Fever ◽

Western Immunoblotting ◽

Western Immunoblot ◽

Chronic Q Fever

Western immunoblotting was used to compare the immune response toCoxiella burnetiiphase I and phase II antigens of humans with acute and chronic Q fever with that of infected cats, rabbits, cows and raccoons. The cats, rabbits, cows and raccoons had an immunoblot profile similar to that of the human with chronic Q fever.

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Truckin' pneumonia—an outbreak of Q fever in a truck repair plant probably due to aerosols from clothing contaminated by contact with newborn kittens

Epidemiology and Infection ◽

10.1017/s0950268800029757 ◽

1989 ◽

Vol 102 (1) ◽

pp. 119-127 ◽

Cited By ~ 56

Author(s):

Thomas J. Marrie ◽

Donald Langille ◽

Vasilia Papukna ◽

Linda Yates

Keyword(s):

Phase I ◽

Phase Ii ◽

Coxiella Burnetii ◽

Attack Rate ◽

Q Fever ◽

The Other ◽

High Antibody ◽

First Case ◽

The Family ◽

Antibody Titres

SUMMARYWe describe an outbreak of Q fever affecting 16 of 32 employees at a truck repair plant. None of the cases were exposed to cattle, sheep or goats. the traditional reservoirs of Q fever. The cases did not work, live on, or visit farms or attend livestock auctions. One of the employees had a cat which gave birth to kittens 2 weeks prior to the first case of Q fever in the plant. The cat owner fed the kittens every day before coming to work as the cat would not let the kittens suckle. Serum from the cat had high antibody titres to phase I and phase IICoxiella burnetiiantigens. The attack rate among the employees where the cat owner worked. 13 of 19 (68%), was higher than that of employees elsewhere, 3 of 13 (28%) [P <0·01]. The cat owner's wife and son also developed Q fever. None of the family members of the other employees with Q fever was so affected.We conclude that this outbreak of Q fever probably resulted from exposure to the contaminated clothing of the cat owner.

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Early Diagnosis and Treatment of Patients with Symptomatic Acute Q Fever Do Not Prohibit IgG Antibody Responses to Coxiella burnetii

Clinical and Vaccine Immunology ◽

10.1128/cvi.00322-12 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1661-1666 ◽

Cited By ~ 8

Author(s):

C. C. H. Wielders ◽

L. M. Kampschreur ◽

P. M. Schneeberger ◽

M. M. Jager ◽

A. I. M. Hoepelman ◽

...

Keyword(s):

Early Diagnosis ◽

Phase I ◽

Phase Ii ◽

Coxiella Burnetii ◽

Q Fever ◽

Antibody Responses ◽

Igg Antibody ◽

Antibody Titers ◽

Acute Q Fever

ABSTRACTLittle is known about the effect of timing of antibiotic treatment on development of IgG antibodies following acute Q fever. We studied IgG antibody responses in symptomatic patients diagnosed either before or during development of the serologic response toCoxiella burnetii. Between 15 and 31 May 2009, 186 patients presented with acute Q fever, of which 181 were included in this retrospective study: 91 early-diagnosed (ED) acute Q fever patients, defined as negative IgM phase II enzyme-linked immunosorbent assay (ELISA) and positive PCR, and 90 late-diagnosed (LD) acute Q fever patients, defined as positive/dubious IgM phase II ELISA and positive immunofluorescence assay (IFA). Follow-up serology at 3, 6, and 12 months was performed using IFA (IgG phase I and II). High IgG antibody titers were defined as IgG phase II titers of ≥1:1,024 together with IgG phase I titers of ≥1:256. At 12 months, 28.6% of ED patients and 19.5% of LD patients had high IgG antibody titers (P= 0.17). No statistically significant differences were found in frequencies of IgG phase I and IgG phase II antibody titers at all follow-up appointments for adequately and inadequately treated patients overall, as well as for ED and LD patients analyzed separately. Additionally, no significant difference was found in frequencies of high antibody titers and between early (treatment started within 7 days after seeking medical attention) and late timing of treatment. This study indicates that early diagnosis and antibiotic treatment of acute Q fever do not prohibit development of the IgG antibody response.

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Seroprevalence of Q fever in small ruminants in the northeast Anatolian region in Turkey

Medycyna Weterynaryjna ◽

10.21521/mw.6522 ◽

2021 ◽

Vol 77 (05) ◽

pp. 6522-2021

Author(s):

PERIHAN SERIFOĞLU BAGATIR ◽

BIRAY OKUMUS ◽

EDIZ KAAN OZGEN ◽

MUSTAFA ULUCAN ◽

BERNA YANMAZ ◽

...

Keyword(s):

Phase I ◽

Coxiella Burnetii ◽

Indirect Elisa ◽

Q Fever ◽

Small Ruminants ◽

Animal Husbandry ◽

Fold Increase ◽

Igg Antibodies ◽

Serum Samples ◽

Goat Population

The aim of our study was to determine the seroepidemiological profile of Q fever in small ruminants in Turkey and to examine its prevalence changes over the years. The study included 573 serum samples taken in 2013 and 472 samples taken in 2017 from animals in mixed herds of sheep and goats from 84 farms in Northeast Anatolia. Phase I and phase II IgG antibodies against Coxiella burnetii in serum samples were investigated by IDEXX ELISA (Q fever Ab Test IDEXX Laboratories, USA) indirect ELISA kits. Seroprevalence of Coxiella burnetii IgG in Artvin, Gümüşhane and Iğdır provinces was 5.6% in sheep, 1.8% in goats and 4.5% in total in 2013. In contrast, it was 24.4% in sheep, 1.1% in goats and 20.1% in total in 2017. According to the total seroprevalence rates calculated by including both sheep and goat population, it was seen that the province with the highest seroprevalence change in these animals was Iğdır with a 7.3-fold increase. Herd-level seroprevalence was 29.4% in 2013 and 57.6% in 2017. According to these results, the C. burnetii IgG seroprevalence nearly doubled after four years. This increase has been evaluated as a major risk for animal and human health as well as for the livestock economy in Northeastern Anatolia, where animal husbandry is intense.

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Culture under normoxic conditions and enhanced virulence of phase II Coxiella burnetii transformed with a RSF1010-based shuttle vector

10.1101/747220 ◽

2019 ◽

Cited By ~ 1

Author(s):

Shengdong Luo ◽

Zemin He ◽

Zhihui Sun ◽

Yonghui Yu ◽

Yongqiang Jiang ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Coxiella Burnetii ◽

Q Fever ◽

Shuttle Vector ◽

Axenic Culture ◽

Hypoxic Condition ◽

Kanamycin Resistance ◽

Temperature Sensitive ◽

Egfp Gene

AbstractCoxiella burnetii is a Gram-negative, facultative intracellular microorganism that can cause acute or chronic Q fever in human. It was recognized as an obligate intracellular organism until the revolutionary design of an axenic cystine culture medium (ACCM). Present axenic culture of C. burnetii strictly requires a hypoxic condition (<10% oxygen). Here we investigated the normoxic growth of C. burnetii strains in ACCM-2 with or without tryptophan supplementation. Three C. burnetii strains - Henzerling phase I, Nine Mile phase II and a Nine Mile phase II transformant, were included. The transformant contains a pMMGK plasmid that is composed of a RSF1010 ori, a repABC operon, an eGFP gene and a kanamycin resistance cassette. We found that, under normoxia if staring from an appropriate concentration of fresh age inocula, Nine Mile phase II can grow significantly in ACCM-2 with tryptophan, while the transformant can grow robustly in ACCM-2 with or without tryptophan. In contrast, long-term frozen stocks of phase II and its transformant, and Henzerling phase I of different ages had no growth capability under normoxia under any circumstances. Furthermore, frozen stocks of the transformant consistently caused large splenomegaly in SCID mice, while wild type Nine Mile phase II induced a lesser extent of splenomegaly. Taken together, our data show that normoxic cultivation of phase II C. burnetii can be achieved under certain conditions. Our data suggests that tryptophan and an unknown temperature sensitive signal are involved in the expression of genes for normoxic growth regulated by quorum sensing in C. burnetii.

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Draft Genome Sequence of Coxiella burnetii Historical Strain Leningrad-2, Isolated from Blood of a Patient with Acute Q Fever in Saint Petersburg, Russia

Genome Announcements ◽

10.1128/genomea.01464-17 ◽

2018 ◽

Vol 6 (3) ◽

Author(s):

Olga Freylikhman ◽

Artem Kiselev ◽

Sergey Kazakov ◽

Alexey Sergushichev ◽

Yulia Panferova ◽

...

Keyword(s):

Phase I ◽

Genome Sequence ◽

Coxiella Burnetii ◽

Guinea Pigs ◽

Q Fever ◽

Draft Genome ◽

Draft Genome Sequence ◽

Saint Petersburg ◽

Acute Q Fever

ABSTRACT This is the announcement of a draft genome sequence of Coxiella burnetii strain Leningrad-2, phase I. The strain, which is mildly virulent in infected guinea pigs, was isolated in 1957 from the blood of a patient with acute Q fever in Leningrad (now Saint Petersburg), Russia.

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