Abstract
This study aimed to explore if viable C. burnetii avirulent Nine Mile phase II (NMII) can elicit protective immunity against virulent NM phase I (NMI) infection. Interestingly, mice immunized with viable NMII elicited significant protection against NMI infection at different time points post-immunization. Viable NMII induced a dose-dependent NMI-specific IgG response in mice, but all doses of NMII-immunized mice conferred a similar level of protection. Comparing different routes of immunization indicated that intranasally immunized mice showed significantly higher levels of protection than other immunization routes. The observation that viable NMII induced a similar level of long-term protection against NMI challenge as the formalin-inactivated NMI vaccine (PIV) suggests that viable NMII bacteria can induce a similar level of long-term protection against virulent NMI challenge as the PIV. Viable NMII also induced significant protection against challenge with virulent Priscilla and Scurry strains, suggesting that viable NMII can elicit broad protection. Immune sera and splenocytes from viable NMII-immunized mice are protective against NMI infection, but immune serum-receiving mice did not control NMI replication. Additionally, viable NMII conferred a comparable level of protection in wild-type, CD4+ T cell-deficient, and CD8+ T cell-deficient mice, and partial protection in B cell-deficient mice. However, NMII-immunized T cell-deficient mice were unable to prevent C. burnetii replication. Thus, both B cells and T cells are required for viable NMII-induced protective immunity but T cells may play a critical role. Collectively, this study demonstrates the feasibility of using avirulent NMII as a live attenuated vaccine against human Q fever.
Highlights
Coxiella burnetii is an obligate intracellular bacterium that causes flu-like zoonosis and Q-fever
To explore whether viable avirulent Nine Mile phase II (NMII) can interfere the infection caused by the virulent NM phase I (NMI), we examined i) if coinfection of mice with NMI and NMII would significantly affect the ability of NMI to cause disease and ii) if priming of mice with alive NMII before infection with NMI would alter the infection caused by the virulent NMI
The findings suggest that the viable non-pathogenic NMII bacteria may be capable of inducing protective immunity against virulent C. burnetii infection
Summary
Coxiella burnetii is an obligate intracellular bacterium that causes flu-like zoonosis and Q-fever. Serological assays are used to diagnose acute infection and most of these patients recover after treatment with 100 mg dose of doxycycline twice a day for 2 weeks [6]. In case of chronic Q-fever, a 100-mg dose of doxycycline was administered twice daily, 200 mg hydroxychloroquine three times a day for a minimum of 18 months and longer in immune-compromised patients [7]. To prevent these complications, a wide-range preventive vaccine is critical, for those at risk due to occupation, such as veterinarians, meat-processing plant workers, sheep and dairy workers, livestock farmers, and researchers at facilities housing sheep
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