Characterization of protective immune responses against Neisseria gonorrhoeae induced by intranasal immunization with adhesion and penetration protein.

Drug-resistant N. gonorrhoeae is an urgent threat to global public health, and vaccine development is the best long-term strategy for controlling gonorrhea. We have previously shown that adhesion and penetration protein (App) play a role in the adhesion, invasion, and reproductive tract colonization of N. gonorrhoeae. Here, we describe the immune response induced by intranasal immunization with passenger and translocator fragments of App. The recombinant App passenger and translocator fragments induced high titers of IgG and IgA antibodies in serum and vaginal washes. Antibodies produced by App passenger and the combination of passenger and translocator mediated the killing of N. gonorrhoeae via serum bactericidal activity and opsonophagocytic activity, whereas antisera from translocator-immunized groups had lower bactericidal activity and opsonophagocytic activity. The antisera of the App passenger and translocator, alone and in combination, inhibited the adhesion of N. gonorrhoeae to cervical epithelial cells in a concentration-dependent manner. Nasal immunization with App passenger and translocator fragments alone or in combination induced high levels of IgG1, IgG2a, and IgG2b antibodies and stimulated mouse splenocytes to secrete cytokines IFN-γ and IL-17A, suggesting that Th1 and Th17 cellular immune responses were activated. In vivo experiments have shown that immune App passenger and transporter fragments can accelerate the clearance of N. gonorrhoeae in the vagina of mice. These data suggest that the App protein is a promising N. gonorrhoeae vaccine antigen.

16S ribosomal assay for early diagnosis of gonococcal meningitis with negative CSF culture: A case report.

Gonococcal meningitis is an exceedingly rare infectious disease, and if not diagnosed and treated in time, it can be severe. We present a case of gonococcal meningitis occurring in a 31-year old healthy woman. She was admitted with fever and persistent headache without urogenital symptoms. Blood cultures were positive and identified as N.gonorrhoeae, but CSF and cervical secretions cultures were both negative. Further testing confirmed the presence of N.gonorrhoeae by 16S ribosomal gene amplification and sequencing in all samples. These results suggest that the case may be a disseminated infection caused by untreated gonorrhea. Our case also shows that nucleic acid detection plays an important role in the rapid and precise diagnosis of gonococcal meningitis and in finding the origin of the pathogen.

Subcutaneous immunization with the fusion protein ΔA146Ply-SP0148 confers protection against Streptococcus pneumoniae infection.

Pneumococcal SP0148 and pneumolysin (Ply) derivatives are important vaccine candidates. SP0148 is a conserved lipoprotein with high immunogenicity produced by Streptococcus pneumoniae. We have previously demonstrated that SP0148 can confer protection against fatal infections caused by S. pneumoniae. ΔA146Ply is a noncytotoxic mutant of Ply that retains the TLR4 agonistic effect and has mucosal and subcutaneous adjuvant activities suggested to induce protective immunity against S. pneumoniae infection. In this study, we constructed the fusion protein ΔA146Ply-SP0148, composed of ΔA146Ply and SP0148, and evaluated the immunoprotective effect of the fusion protein. When mice were subcutaneously immunized with the fusion protein ΔA146Ply-SP0148, high levels of anti-ΔA146Ply and anti-SP0148 IgG antibodies were induced in the serum. Specific antibodies can bind to a variety of different serotypes of S. pneumoniae. Compared with mice immunized with ΔA146Ply and SP0148 alone, mice immunized subcutaneously with the fusion protein ΔA146Ply-SP0148 with Al(OH)3 had a higher survival rate when challenged by a lethal dose of S. pneumoniae, and they also had significantly lower lung bacterial loads and milder lung inflammation. In addition, mice immunized subcutaneously with the fusion protein ΔA146Ply-SP0148 stimulated strong Th1, Th2, and Th17 cell responses. In summary, these results suggest that subcutaneous immunization with the ΔA146Ply-SP0148 fusion protein can protect mice against fatal pneumococcal infection and lung infection. The fusion protein ΔA146ply-SP0148 can be a new pneumococcal vaccine target.