Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity
Carrie M. Long,
Paul A. Beare,
Diane C. Cockrell,
Jonathan Fintzi,
Mahelat Tesfamariam,
Carl I. Shaia,
Robert A. Heinzen
Affiliations
Carrie M. Long
Coxiella Pathogenesis Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Paul A. Beare
Coxiella Pathogenesis Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Diane C. Cockrell
Coxiella Pathogenesis Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Jonathan Fintzi
Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Mahelat Tesfamariam
Coxiella Pathogenesis Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Carl I. Shaia
Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Robert A. Heinzen
Coxiella Pathogenesis Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Abstract Coxiella 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.
