In this study, we demonstrated that the 40-kDa outer membrane protein of Porphyromonas gingivalis (40-kDa OMP) nasally administered with a nontoxic chimeric adjuvant that combines the A subunit of mutant cholera toxin E112K with the pentameric B subunit of heat-labile enterotoxin from enterotoxigenic Escherichia coli (mCTA/LTB) elicited a long-term protective immune response. Immunization with the 40-kDa OMP and mCTA/LTB induced high levels of 40-kDa-OMP-specific immunoglobulin G (IgG) and IgA antibodies (Abs) in sera and elicited a significant IgA anti-40-kDa OMP Ab response in saliva. These Ab responses were maintained for at least 1 year after the immunization. Although using adjuvant mCTA/LTB gave Ab responses in the saliva comparable to those obtained using native cholera toxin (nCT) as the adjuvant, the levels of total IgE and 40-kDa-OMP-specific IgE Abs as well as interleukin-4 levels induced by the immunization with mCTA/LTB were lower than those induced by the immunization with nCT. Importantly, IgG Abs generated by nasal immunization with the 40-kDa OMP plus mCTA/LTB inhibited the coaggregation and hemagglutinin activities of P. gingivalis. Furthermore, the mice given nasal 40-kDa OMP plus mCTA/LTB showed a significant reduction of alveolar bone loss caused by oral infection with P. gingivalis even 1 year after the immunization compared to the loss in unimmunized mice. Because mCTA/LTB is nontoxic, nasally administered 40-kDa OMP together with mCTA/LTB should be an effective and safe mucosal vaccine against P. gingivalis infection in humans and may be an important tool for the prevention of chronic periodontitis.Chronic periodontitis is a common oral inflammatory disease that causes the breakdown of periodontal tissue, including the resorption of alveolar bone, and as a consequence, tooth loss (8). Furthermore, recent studies have suggested that chronic periodontitis influences systemic conditions such as cardiovascular diseases, diabetes, and osteoporosis (5,10,19,28,39,41,45). Hence, the prevention of periodontitis is important for both oral and systemic health.Porphyromonas gingivalis, a gram-negative anaerobic bacterium, has been shown previously to be one of the major pathogens in chronic periodontitis. The colonization of gingival tissues by this bacterium is considered to be the first step in the pathogenic process of periodontal disease resulting in tissue destruction (24, 37). Molecules such as fimbriae, hemagglutinins, aggregation factors, and lipopolysaccharides responsible for colonization have been identified previously as virulence factors (24,37). An outer membrane protein having a molecular mass of 40 kDa produced by P. gingivalis (40-kDa OMP) is a key virulence factor involved in the coaggregation activity of P. gingivalis (23). Furthermore, this OMP has been shown previously to be a hemin-binding protein (49). The 40-kDa OMP resides both on the cell surface and in extracellular vesicles and is found on many strains of P. gingivalis (1,22,23,47).Previous studies have demonstrated that ...

Tuberculosis caused by Mycobacterium tuberculosis is responsible for nearly two million deaths every year globally. A single licensed vaccine derived from Mycobacterium bovis, bacille CalmetteGuerin (BCG) administered perinatally as a prophylactic vaccine has been in use for over 80 years and confers substantial protection against childhood tuberculous meningitis and miliary tuberculosis. However, the BCG vaccine is virtually ineffective against the adult pulmonary form of tuberculosis that is pivotal in the transmission of tuberculosis that has infected almost 33% of the global population. Thus, an effective vaccine to both prevent tuberculosis and reduce its transmission is urgently needed. We have generated a multi-valent, vectored vaccine candidate utilizing the modified virus Ankara (MVA) strain of vaccinia virus to tandemly express five antigens, ESAT6, Ag85A, Ag85B, HSP65 and Mtb39A of Mycobacterium tuberculosis that have been reported to be protective individually in certain animal models together with an immunostimulatory cytokine interleukin 15 (MVA/IL-15/5Mtb). Although, immunological correlates of protection against tuberculosis in humans remain to be established, we demonstrate that our vaccine induced comparable CD4 + T cell and greater CD8 + T cell and antibody responses against Mycobacterium tuberculosis in vaccinated mice in a direct comparison with the BCG vaccine and conferred protection against an aerogenic challenge of M. tuberculosis, thus warranting its further preclinical development.

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