Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines.

Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way to prevent tularemia. However, there are no Food and Drug Administration (FDA)-approved Ft vaccines thus far due to safety concerns. Herein, three membrane proteins of Ft, Tul4, OmpA, and FopA, and a molecular chaperone, DnaK, were identified as potential protective antigens using a multifactor protective antigen platform. Moreover, the recombinant DnaK, FopA, and Tul4 protein vaccines elicited a high level of IgG antibodies but did not protect against challenge. In contrast, protective immunity was elicited by a replication-defective human type 5 adenovirus (Ad5) encoding the Tul4, OmpA, FopA, and DnaK proteins (Ad5-Tul4, Ad5-OmpA, Ad5-FopA, and Ad5-DnaK) after a single immunization, and all Ad5-based vaccines stimulated a Th1-biased immune response. Moreover, intramuscular and intranasal vaccination with Ad5-Tul4 using the prime-boost strategy effectively eliminated Ft lung, spleen and liver colonization and provided nearly 80% protection against intranasal challenge with the Ft live vaccine strain (LVS). Only intramuscular, not intranasal vaccination, with Ad5-Tul4 protected mice from intraperitoneal challenge. This study provides a comprehensive comparison of protective immunity against Ft provided by subunit or adenovirus-vectored vaccines and suggests that mucosal vaccination with Ad5-Tul4 may yield desirable protective efficacy against mucosal infection, while intramuscular vaccination offers greater overall protection against intraperitoneal tularemia.

The formation mechanism of the beta-TCP phase in synthetic fluorohydroxyapatite with different fluorine contents.

Synthetic hydroxyapatite (HAP) and fluorohydroxyapatite (F(x)AP) products may form the beta-tricalcium phosphate (beta-TCP) phase in a calcination process. The beta-TCP phase has a greater tendency for degradation in vivo than HAP and F(x)AP. Hence, controlling the content of the beta-TCP phase in the apatite is a pivotal factor to affect their lifetime and stability in vivo. It is particularly important to explore the formation mechanism of the beta-TCP phase in synthetic apatite. In this work, F(x)AP products with a chemical composition of Ca(10)(PO(4))(6)(OH)(2-x)F(x) are synthesized, with x = 0, 0.4, 0.8, 1.2, 1.6 and 2.0, using a precipitation method and a calcination process. The effect of fluorine substitution for hydroxyl is investigated by using x-ray diffraction analysis, Fourier transform infrared spectroscopy, and thermogravimetry and differential thermal analysis. The results show that addition of fluorine forms F(x)AP that exhibits high thermal stability. The beta-TCP phase produced as a result of the structural refinement by heat treatment is gradually reduced and dramatically suppressed with the fluorine content.