Preclinical Animal Models for Q Fever Vaccine Development

Tesfamariam, Mahelat; Binette, Picabo; Long, Carrie M.

doi:10.3389/fcimb.2022.828784

Cited by 7 publications

(2 citation statements)

References 52 publications

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“…In this study, we tested vaccines created from OSP derived from C. burnetii grown in axenic culture media, and OSP grown in embryonated eggs. Guinea pigs were selected to test the vaccines as infection mimics Q fever in humans with respect to symptoms, duration of illness and recovery [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

An O-Specific Polysaccharide/Tetanus Toxoid Conjugate Vaccine Induces Protection in Guinea Pigs against Virulent Challenge with Coxiella burnetii

et al. 2022

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Q fever is caused by the bacterium Coxiella burnetii and is spread to humans from infected animals especially goats, sheep and cattle, predominantly when giving birth. There is an effective human vaccine (Q-VAX) against Q fever, and although Q fever is a worldwide problem, the vaccine is only used in Australia due to difficulties associated with its use and the risk of adverse reactions. The desire to protect humans, particularly farmers and abattoir workers, from Q fever prompted the development of a new safe and effective human vaccine without all the difficulties associated with the current vaccine. Candidate vaccines were prepared using purified O-specific polysaccharide (OSP) extracted from the lipopolysaccharide of virulent (phase 1) C. burnetii, strain Nine Mile, which was then conjugated to a tetanus toxoid (TT) carrier protein. Two vaccines were prepared using OSP from C. burnetii grown in embryonated eggs (vaccine A) and axenic media (vaccine B). Vaccines with or without alum adjuvant were used to vaccinate guinea pigs, which were later challenged by intranasal inoculation with virulent C. burnetii. Both vaccines protected guinea pigs from fever and loss of weight post challenge. Post-mortem samples of the spleen, liver and kidney of vaccinated guinea pigs contained substantially less C. burnetii DNA as measured by PCR than those of the unvaccinated control animals. This study demonstrated that a C. burnetii OSP-TT conjugate vaccine is capable of inducing protection against virulent C. burnetii in guinea pigs. Additionally, OSP derived from C. burnetii grown in axenic media compared to OSP from embryonated eggs is equivalent in terms of providing a protective immune response.

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Section: Introductionmentioning

confidence: 99%

An O-Specific Polysaccharide/Tetanus Toxoid Conjugate Vaccine Induces Protection in Guinea Pigs against Virulent Challenge with Coxiella burnetii

et al. 2022

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“…Although human Q fever vaccine-associated DTH reactions have not been well-characterized immunologically, clinical observations suggest a biphasic DTH response ( 13 ), possibly involving tuberculin-type and granulomatous DTH characterized by two peaks of skin reactivity (days 1-2 and 9) ( 14 ). Currently, guinea pig models are the most well-developed ( 15 ), with animals displaying delayed erythema and induration kinetics ( 16 ) along with abscess and granuloma formation ( 17 ). Importantly, quantifiable erythema and induration typically occur no earlier than 7 days following skin testing in guinea pig models, suggesting that the ensuing response is primarily that of late-phase or granulomatous DTH.…”

Section: Introductionmentioning

confidence: 99%

Murine Q Fever Vaccination Model Reveals Sex Dimorphism in Early Phase Delayed-Type Hypersensitivity Responses

et al. 2022

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Delayed-type hypersensitivity (DTH) responses to microbial vaccines and related components are a major roadblock for widespread licensing of whole cell vaccines such as that of Q fever. Q fever is a zoonotic disease caused by the intracellular bacterium Coxiella burnetii. The only currently licensed vaccine, Q-Vax®, is a whole cell inactivated formulation that is associated with a potentially severe dermal post vaccination DTH response in previously sensitized individuals. To investigate the underlying immunologic mechanisms of this response and better represent the early-phase DTH response observed in humans, a murine sensitization and skin testing model was developed and employed. Female C57Bl/6J mice displayed the most robust early-phase DTH responses following sensitization and elicitation compared to their male counterparts and other mouse strains. Immunologic responses were measured within the skin, draining lymph nodes, and serum following both sensitization and elicitation with Q fever whole cell vaccines. Local immunologic responses in the dermis were characterized by inflammation primarily involving neutrophils, macrophages, and T cells. Secondary lymphoid organ profiling revealed distinct immunological signatures following both sensitization and elicitation with a sex-based dichotomy in T cell phenotypes and antigen presenting cell numbers. Beyond providing a post-Q fever vaccination DTH model that recapitulates early-phase DTH events, these data suggest that sex is a primary factor influencing the magnitude and composition of the ensuing response.

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Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever

Sam,

Plain,

Chen

et al. 2024

Adv Healthcare Materials

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Coxiella burnetti is an intracellular bacterium that causes Q fever, a disease of worldwide importance. Q‐VAX®, the approved human Q fever vaccine, is a whole cell vaccine associated with safety concerns. Here we developed a safe particulate subunit vaccine candidate that is ambient‐temperature stable and can be cost‐effectively manufactured. We bioengineered endotoxin‐free Escherichia coli to efficiently self‐assemble biopolymer particles (BPs) that are densely coated with either strings of 18 T‐cell epitopes (COX‐BP) or two full‐length immunodominant antigens (YbgF‐BP‐Com1) all derived from C. burnetii. BP vaccine candidates were ambient‐temperature stable. Safety and immunogenicity were confirmed in mice and guinea pig models. YbgF‐BP‐Com1 elicited specific and strong humoral immune responses in guinea pigs with IgG titers that were at least 1000 times higher than those induced by Q‐VAX®. BP vaccine candidates were not reactogenic. After challenge with C. burnetii, YbgF‐BP‐Com1 vaccine led to reduced fever responses and pathogen burden in the liver and the induction of proinflammatory cytokines IL‐12 and IFN‐γ inducible protein (IP‐10) when compared to negative control groups. These data suggested that YbgF‐BP‐Com1 induces functional immune responses reducing infection by C. burnetii. Collectively, our findings illustrate the potential of BPs as an effective antigen carrier for Q fever vaccine development.This article is protected by copyright. All rights reserved

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Preclinical Animal Models for Q Fever Vaccine Development

Cited by 7 publications

References 52 publications

An O-Specific Polysaccharide/Tetanus Toxoid Conjugate Vaccine Induces Protection in Guinea Pigs against Virulent Challenge with Coxiella burnetii

An O-Specific Polysaccharide/Tetanus Toxoid Conjugate Vaccine Induces Protection in Guinea Pigs against Virulent Challenge with Coxiella burnetii

Murine Q Fever Vaccination Model Reveals Sex Dimorphism in Early Phase Delayed-Type Hypersensitivity Responses

Synthetic Particulate Subunit Vaccines for the Prevention of Q Fever

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