scholarly journals Q Fever Vaccine Development: Current Strategies and Future Considerations

Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1223
Author(s):  
Carrie Mae Long
Keyword(s):  
Vaccine Development ◽  
Q Fever ◽  
Febrile Illness ◽  
Cell Vaccine ◽  
Environmental Persistence ◽  
Post Vaccination ◽  
Area Of Interest ◽  
Whole Cell Vaccine ◽  
History Of ◽  
Acute Q Fever

Q fever is a zoonotic disease caused by the intracellular pathogen Coxiella burnetii. This disease typically manifests as a self-limiting, febrile illness known as acute Q fever. Due to the aerosol transmissibility, environmental persistence, and infectivity of C. burnetii, this pathogen is a notable bioterrorism threat. Despite extensive efforts to develop next-generation human Q fever vaccines, only one vaccine, Q-Vax®, is commercially available. Q-Vax® is a phase I whole-cell vaccine, and its licensed use is limited to Australia, presumably due to the potential for a post-vaccination hypersensitivity response. Pre-clinical Q fever vaccine development is a major area of interest, and diverse approaches have been undertaken to develop an improved Q fever vaccine. Following a brief history of Q fever vaccine development, current approaches will be discussed along with future considerations for an improved Q fever vaccine.

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

npj Vaccines ◽  
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.

scholarly journals Clinical characteristics of acute Q fever patients in South Korea and time from symptom onset to serologic diagnosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jung Yeon Heo ◽  
Young Wha Choi ◽  
Eun Jin Kim ◽  
Seung Hun Lee ◽  
Seung Kwan Lim ◽  
...  
Keyword(s):  
South Korea ◽  
Symptom Onset ◽  
Clinical Characteristics ◽  
Q Fever ◽  
Febrile Illness ◽  
Serologic Diagnosis ◽  
Animal Contact ◽  
History Of ◽  
Acute Q Fever ◽  
High Phase

Abstract Background Acute Q fever usually presents as a nonspecific febrile illness, and its occurrence is rapidly increasing in South Korea. This study investigated the clinical characteristics of acute Q fever patients in South Korea and the time from symptom onset to serologic diagnosis. The clinical courses were examined according to antibiotic treatment. Methods Data of patients diagnosed with acute Q fever at Chungbuk National University Hospital between January 2015 and February 2018 were retrospectively collected. Demographic and epidemiologic data were reviewed. The time from symptom onset to serologic diagnosis by an immunofluorescence assay (IFA) was analyzed. Clinical courses and the percentage of patients with a high phase I immunoglobulin G titer (≥ 1:1024) were compared between patients administered antibiotics with anti-Coxiella burnetii activity and patients not administered such antibiotics. Results Forty-eight patients (median age: 51.5 years) were included. Most were male (95.8%) and had no history of animal contact (91.7%). The median time from illness onset to serologic diagnosis was 21 days. Thirty-nine patients received antibiotics with anti-C. burnetii activity. The length of hospital stay and fever duration did not significantly differ between patients who received antibiotics with anti-C. burnetii activity (7 and 15 days) and those who did not (5 and 8 days) (P = 0.110 and P = 0.137, respectively). The percentage of patients with a high phase I immunoglobulin G titer (≥ 1:1024) did not significantly differ between patients who received antibiotics with anti-C. burnetii activity and those who did not (P = 0.340). Conclusions Most acute Q fever patients had a nonspecific febrile illness with mild elevation of transaminases and no history of animal contact or occupational risk. The time from symptom onset to a positive IFA test was longer than the fever duration in most acute Q fever patients. Consequently, it may be difficult for clinicians to serologically diagnose acute Q fever. However, inappropriate antibiotic treatment was not associated with prolongation of symptoms or progression to chronic Q fever.

scholarly journals Coxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman Primates

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
A. E. Gregory ◽  
E. J. van Schaik ◽  
K. E. Russell-Lodrigue ◽  
A. P. Fratzke ◽  
J. E. Samuel
Keyword(s):  
Animal Models ◽  
Coxiella Burnetii ◽  
Guinea Pigs ◽  
Nonhuman Primates ◽  
Q Fever ◽  
Febrile Illness ◽  
Cell Vaccine ◽  
Infection Model ◽  
Atypical Pneumonia ◽  
Content Type

ABSTRACT Coxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against C. burnetii remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible C. burnetii aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with C. burnetii Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to C. burnetii aerosol transmission.

scholarly journals The natural history of acute Q fever: a prospective Australian cohort

QJM ◽  
2016 ◽  
Vol 109 (10) ◽  
pp. 661-668 ◽  
Author(s):  
B. Hopper ◽  
B. Cameron ◽  
H. Li ◽  
S. Graves ◽  
J. Stenos ◽  
...  
Keyword(s):  
Natural History ◽  
Q Fever ◽  
History Of ◽  
Australian Cohort ◽  
Acute Q Fever

scholarly journals Whole-cell vaccine of Streptococcus agalactiae in Oreochromis sp. with immersion method

2015 ◽  
Vol 13 (1) ◽  
pp. 83 ◽  
Author(s):  
, Sukenda ◽  
Trian Rizky Febriansyah ◽  
Sri Nuryati
Keyword(s):  
Water Quality ◽  
Streptococcus Agalactiae ◽  
Cell Vaccine ◽  
Haematocrit Level ◽  
Immersion Method ◽  
Post Vaccination ◽  
Whole Cell ◽  
Whole Cell Vaccine ◽  
Average Body ◽  
Average Body Weight

<p class="NoParagraphStyle" align="center"><strong>ABSTRACT</strong></p><p class="NoParagraphStyle" align="center"><strong> </strong></p><p>The study was aimed to evaluate the efficacy of formalin-killed non-hemolytic <em>Streptococcus agalactiae </em>N14G and NK1 isolates whole-killed vaccine to prevent streptococcosis in tilapia. Ten fishes were reared in a tank 60x30x35 cm3 with an average body weight at 10.79±0.99 g. Fish was vaccinated through bath immersion at a concentration of 109 cfu/mL. Fish was subsequently challenged by intraperitonial injection of <em>Streptococcus agalactiae </em>105 cfu/mL at 11 days post-vaccination. Parameters observed were survival, relative percent survival (RPS), total leukocyte, phagocytic activity, antibody titer, total erythrocyte, haemoglobin level, haematocrit level, dan water quality. Samplings were performed in day-0, 20, and 30 after vaccination. Both vaccines have shown higher survival (60%) and RPS (40%) when challenged with pathogenic <em>Streptococcus </em>N14G isolates than other treatments. Based on RPS percentage observed, those vaccine were still not sufficiently effective to combat <em>S. agalactiae </em>infection.</p><p> </p><p>Keywords: tilapia, bath immersion, <em>Streptococcus agalactiae</em>, whole-cell vaccine</p><br /><p class="NoParagraphStyle"><strong> </strong></p><p class="NoParagraphStyle"><strong><br /></strong></p><p class="NoParagraphStyle" align="center"><strong>ABSTRAK</strong></p><p class="NoParagraphStyle"> </p><p>Penelitian ini bertujuan untuk mengevaluasi efikasi vaksin <em>formalin-killed cell Streptococcus agalactiae </em>tipe isolat nonhemolitik N14G dan NK1 se utuh yang diberikan melalui perendaman dalam mencegah penyakit streptococcosis pada ikan nila. Ikan nila yang digunakan memiliki bobot 10,79±0,99 g, dipelihara sebanyak sepuluh ekor dalam akuarium ukuran 60x30x35 cm3. Ikan divaksinasi dengan metode perendaman dengan dosis 109 cfu/mL. Uji tantang dilakukan pada hari ke-11 pascavaksinasi dengan dosis 105 cfu/mL. Parameter yang diamati meliputi sintasan (SR), sintasan relatif/<em>relative percent surviva</em>l (RPS), total leukosit, aktivitas fagositik, titer antibodi, total eritrosit, kadar hemoglobin, kadar hematokrit, dan kualitas air. Pengamatan parameter dilakukan pada hari ke-0, ke-10, ke-20, dan ke-30. Hasil penelitian menunjukkan perlakuan kedua vaksin yang diinfeksi bakteri patogen isolat N14G memberikan nilai sintasan dan nilai RPS tertinggi dibanding perlakuan lainnya. Nilai sintasan dan RPS kedua perlakuan tersebut adalah 60% dan 40%. Nilai RPS yang cukup kecil menunjukkan vaksin yang diberikan masih kurang efektif untuk mencegah infeksi bakteri <em>S. agalactiae</em>.</p><p> </p><p>Kata kunci: ikan nila, perendaman, <em>Streptococcus agalactiae</em>, vaksin sel utuh</p>

A Survey of Acute Q Fever among Patients with Brucellosis-Like and Atypical Pneumonia Symptoms Who Are Referred to Qaemshahr Razi Hospital in Northern Iran (2014-2015)

2016 ◽  
Vol 9 (4) ◽  
pp. 225 ◽  
Author(s):  
Roya Ghasemian ◽  
Ehsan Mostafavi ◽  
Saber Esmaeili ◽  
Narges Najafi ◽  
Sara Arabsheybani
Keyword(s):  
Risk Factors ◽  
Dairy Products ◽  
Q Fever ◽  
Atypical Pneumonia ◽  
Mazandaran Province ◽  
Northern Iran ◽  
Previous Infection ◽  
History Of ◽  
Acute Q Fever ◽  
Animal Care

<p><strong>INTRODUCTION</strong><strong>:</strong> Coxiella burnetii is the etiologic agent of the zoonotic disease of Q fever which causes lots of morbidities and mortalities every year. The main route of human infection is inhalation of contaminated aerosols; however, consumption of contaminated dairy products is the second cause. Mazandaran province is one of the main livestock centers of the country and consumption of raw dairy in the region is quite common. There isn’t any data about Q fever incidence in this region. It seems that most cases are undiagnosed. Our main target is to prove existence of Q fever human cases in Mazandaran province. We evaluated suspect Q fever cases to demonstrate its incidence and identify the risk factors.</p><p><strong>MATERIAL </strong><strong>&amp; METHODS</strong>: In this cross-sectional study, 56 Patients including 36 patients with brucellosis-like systemic symptoms identified by negative Wright, Coomb's Wright and 2-mercaptoethanol tests as well as 20 patients with symptoms of atypical pneumonia who did not respond to conventional therapy were enrolled. At the beginning of hospitalization and 3-4 weeks later, 10cc blood was obtained from each of 56 patients who referred for a second blood sampling. Demographic, epidemiological, and clinical manifestations of Q fever and clinical changes were completed for each patient. The samples were evaluated quantitatively in terms of the presence of phase II IgG antibodies against Coxiella burnetii by ELISA method. Acute Q fever was confirmed by line-sero conversion (change of antibody from negative to positive) or fourfold antibody rising titer in each patient. The presence of primary and secondary seropositive samples and absence of line-sero conversion (change of antibody from negative to positive) or fourfold increase in antibody titer was considered as previous infection.</p><p><strong>RESULTS</strong><strong>:</strong> The prevalence rate of acute Q fever in 56 patients with 2nd blood sample was 5.3%. There was no history of tick bite, while in 100% of cases there were risk factors such as a history of residence near animal care centers as well as a history of consumption of raw dairy products (P = 0/001). 23.2% had a previous history of Q fever infection, out of which 25.8% lived in rural areas. Among people with risk factors of keeping domestic animals, living close to animal care centers and animal abortion, the prevalence rate of previous infection was higher compared to those who did not have these risk factors.</p><p><strong>CONCLUSION</strong><strong>: </strong>Since most of the patients with acute Q fever have no specific symptom, health care providers do not suspect acute Q fever disease. In this study, it was demonstrated that infection is either directly or indirectly associated with increase in environmental risk factors including contact with livestock and its products. Our study proved that Q fever is endemic in Mazandaran province. In order to have an accurate diagnosis and proper management, clinicians should be aware of existence of this disease in the region. Because of the climate of northern Iran and easy transportation of contaminated particles, appropriate measures should be taken to control and prevent this disease.</p>

scholarly journals Epidemiological, clinical and laboratory characteristics of acute Q fever in an endemic area in Israel, 2006–2016

2019 ◽  
Vol 147 ◽  
Author(s):  
S. Reisfeld ◽  
S. Hasadia Mhamed ◽  
M. Stein ◽  
M. Chowers
Keyword(s):  
Endemic Area ◽  
Q Fever ◽  
Febrile Illness ◽  
Definite Diagnosis ◽  
Febrile Patient ◽  
Rural Regions ◽  
Historical Cohort ◽  
Common Mean ◽  
Acute Q Fever ◽  
Autumn And Winter

AbstractOur purpose was to describe the clinical, epidemiological and laboratory characteristics of patients hospitalised with acute Q fever in an endemic area of Israel. We conducted a historical cohort study of all patients hospitalised with a definite diagnosis of acute Q fever, and compared them to patients suspected to have acute Q fever, but diagnosis was ruled out. A total of 38 patients had a definitive diagnosis, 47% occurred during the autumn and winter seasons, only 18% lived in rural regions. Leucopaenia and thrombocytopaenia were uncommon (16% and 18%, respectively), but mild hepatitis was common (mean aspartate aminotransferase 76 U/l, mean alanine aminotransferase 81 U/l). We compared them with 74 patients in which acute Q fever was ruled out, and found that these parameters were not significantly different. Patients with acute Q fever had a shorter hospitalisation and they were treated more often with doxycycline than those without acute Q fever (6.4vs. 14 days,P= 0.007, 71%vs. 38%,P= 0.001, respectively). In conclusion, acute Q fever can manifest as an unspecified febrile illness, with no seasonality. We suggest that in endemic areas, Q fever should be considered in the differential diagnosis in any febrile patient with risk factors for a persistent infection.

Influenza B, Q Fever and the consequences of febrile illness occurring during Jungle Warfare Training: a clinical and serological study

1989 ◽  
Vol 75 (1) ◽  
pp. 13-18
Author(s):  
M. C. J. Wale
Keyword(s):  
Q Fever ◽  
Febrile Illness ◽  
Influenza B ◽  
Serological Study ◽  
Serological Evidence ◽  
Heat Exhaustion ◽  
Acute Q Fever

AbstractSeventy-one Royal Marines undergoing jungle warfare training were studied clinically and serologically to determine the incidence and consequences of febrile illness. During acclimatisation and the early part of the deployment the incidence of illness having an impact on training was low; during the latter part an outbreak of influenza B occurred, with 25 cases diagnosed clinically. Only 12 of these were confirmed serogically, probably because the outbreak was still in progress when the second samples were taken. A further four subclinical cases were uncovered by the serological study.Five cases of heat exhaustion occurred, one Marine suffering two episodes. Four patients required casevac from the jungle. Three Marines were found to have serological evidence of previous acute Q fever, including the patient who had two episodes of heat exhaustion. This incidence is higher than expected, and warrants further investigation.

scholarly journals TH17-Mediated Protection against Pneumococcal Carriage by a Whole-Cell Vaccine Is Dependent on Toll-Like Receptor 2 and Surface Lipoproteins

2015 ◽  
Vol 22 (8) ◽  
pp. 909-916 ◽  
Author(s):  
K. Moffitt ◽  
A. Howard ◽  
S. Martin ◽  
E. Cheung ◽  
M. Herd ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Protective Efficacy ◽  
Cell Vaccine ◽  
Membrane Localization ◽  
Toll Like Receptor ◽  
Gene Encoding ◽  
Whole Cell ◽  
Interleukin 17A ◽  
Whole Cell Vaccine ◽  
Toll Like Receptor 2

ABSTRACTA pneumococcal whole-cell vaccine (WCV) confers TH17-mediated immunogenicity and reduces nasopharyngeal (NP) carriage in mice. Activation of Toll-like receptor 2 (TLR2) has been shown to be important for generating TH17 responses, and several lipidated pneumococcal proteins have TLR2-activating properties. Here we investigated the roles of TLR2 and lipidation of proteins in WCV-induced interleukin-17A (IL-17A) responses and protection against NP carriage. Immunization ofTlr2−/−mice with WCV conferred significantly lower IL-17A levels and reduced protection against NP carriage, compared to wild-type (WT) mice, suggesting that host TLR2 engagement is required for effective immunity and protection elicited by WCV immunization. Using a WCV with deletion oflgt, the gene encoding the enzyme required for lipidation and membrane attachment of prolipoproteins, we show that lipidation and membrane localization of these proteins are critical for the immunogenicity and protective efficacy of the WCV. To evaluate the roles of diacylglyceryl transferase (Lgt)-mediated processes in the recall of WCV-induced protective responses, we colonized WCV-immunized animals with a strain in whichlgtwas deleted. WCV-immunized animals still had significantly reduced colonization burdens, compared to control animals, which suggests that lipidation and membrane localization of pneumococcal prolipoproteins are less critical for the recall of the immune responses elicited by WCV immunization than for the priming of such responses. Elucidation of underlying immune mechanisms and the optimal characteristics of WCV formulations can help guide vaccine development and enhance our understanding of host-pneumococcus interactions.

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