Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines

Dold, Christina; Zhu, Henderson; Silva-Reyes, Laura; Blackwell, Luke; Linder, Aline; Bewley, Kevin R.; Godwin, Kerry; Fotheringham, Susan; Charlton, Sue; Kim, Young Chan; Pollard, Andrew J.; Rollier, Christine S.

doi:10.1016/j.vaccine.2023.04.012

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…The argument can be made that it is on equal standing with the hexavalent groups, as both hexavalent groups demonstrate significant differences when compared to WCV when looking at either the changes in body weight or temperature, while the monovalent group 6 does not ( Figure 6 ). Although others have demonstrated immunogenicity in generating IgG against LPS ( 62 , 63 ), our data show otherwise, possibly due to the nature of the AddaVAX adjuvant in forming lipid droplets and presenting emulsified antigens in certain orientations, hiding immunogenic epitopes. C. burnetii LPS is the only virulence factor identified in the infection of an immunocompetent animal model and has been acknowledged as a shielding molecule in allowing the pathogen to evade the host immune response ( 64 ).…”

Section: Discussioncontrasting

confidence: 74%

“…C. burnetii NMI LPS has been studied extensively as a virulence factor and potential vaccine candidate. Studies in the past have shown that formalin-inactivated phase II C. burnetii lacking the LPS is a less effective vaccine and fails to protect against challenge and that LPS by itself can confer partial protection ( 43 , 63 ). Mice receiving adoptive transfer of bone marrow-derived dendritic cells (BMDCs) stimulated with whole-cell protein antigen were better protected against C. burnetii challenge after LPS removal ( 73 ).…”

Section: Discussionmentioning

confidence: 99%

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Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge

et al. 2023

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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.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge

et al. 2023

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“…When key immunodominant C. burnetii antigens were used for recombinant ELISAs and compared to commercial ELISAs, several studies revealed significant concordance rates. Ybgf (CBU_0092), also known as cell division coordinator CpoB and involved in the Tol-Pal transport system and synthesis of peptidoglycan, is one of the most investigated antigens for its potential use in human and animal vaccinology and diagnostics ( Dold et al, 2023 ; Vigil et al, 2010 ; Xiong et al, 2012 ). Several studies that have identified Ybgf as an early marker of infection have established that the anti-Coxiella humoral response is localized to this periplasmic protein Beare et al (2008) ; Deringer et al (2011) ; Gerlach et al (2017) .…”

Section: Introductionmentioning

confidence: 99%

Efficiency of recombinant Ybgf in a double antigen-ELISA for the detection of Coxiella antibodies in ruminants

Ferrara,

Colitti,

Gabriela

et al. 2024

Veterinary and Animal Science

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Q fever immunology: the quest for a safe and effective vaccine

Sam,

Stenos,

Graves

et al. 2023

npj Vaccines

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Q fever is an infectious zoonotic disease, caused by the Gram-negative bacterium Coxiella burnetii. Transmission occurs from livestock to humans through inhalation of a survival form of the bacterium, the Small Cell Variant, often via handling of animal parturition products. Q fever manifests as an acute self-limiting febrile illness or as a chronic disease with complications such as vasculitis and endocarditis. The current preventative human Q fever vaccine Q-VAX poses limitations on its worldwide implementation due to reactogenic responses in pre-sensitized individuals. Many strategies have been undertaken to develop a universal Q fever vaccine but with little success to date. The mechanisms of the underlying reactogenic responses remain only partially understood and are important factors in the development of a safe Q fever vaccine. This review provides an overview of previous and current experimental vaccines developed for use against Q fever and proposes approaches to develop a vaccine that establishes immunological memory while eliminating harmful reactogenic responses.

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Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines

Cited by 4 publications

References 56 publications

Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge

Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge

Efficiency of recombinant Ybgf in a double antigen-ELISA for the detection of Coxiella antibodies in ruminants

Q fever immunology: the quest for a safe and effective vaccine

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