Intravaginal Administration of Interleukin 12 during Genital Gonococcal Infection in Mice Induces Immunity to Heterologous Strains of Neisseria gonorrhoeae

Liu, Yingru; Perez, Julianny; Hammer, Laura; Gallagher, Heather C.; Jesus, Magdia De; Egilmez, Nejat K.; Russell, Michael W.

doi:10.1128/msphere.00421-17

Cited by 33 publications

(34 citation statements)

References 38 publications

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“…In general, STI pathogen such as N. gonorrhoeae is able to suppress the host Th-1-driven adaptive immune response by inhibiting the production of interleukin-12 (IL-12) [ 191 ]. In view of that, intravaginal administration of microencapsulated IL-12 was able to reverse the immunosuppression in mice and also promotes the clearance of gonorrhoea infection [ 191 ]. At the same time, Lactobacillus PG demonstrates outstanding immunomodulatory activity in improving host innate immune responses.…”

Section: Peptidoglycan (Pg)mentioning

confidence: 99%

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

2020

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Human vagina is colonised by a diverse array of microorganisms that make up the normal microbiota and mycobiota. Lactobacillus is the most frequently isolated microorganism from the healthy human vagina, this includes Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii. These vaginal lactobacilli have been touted to prevent invasion of pathogens by keeping their population in check. However, the disruption of vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis (BV), sexually transmitted infections (STIs), and vulvovaginal candidiasis (VVC). Predisposing factors such as menses, pregnancy, sexual practice, uncontrolled usage of antibiotics, and vaginal douching can alter the microbial community. Therefore, the composition of vaginal microbiota serves an important role in determining vagina health. Owing to their Generally Recognised as Safe (GRAS) status, lactobacilli have been widely utilised as one of the alternatives besides conventional antimicrobial treatment against vaginal pathogens for the prevention of chronic vaginitis and the restoration of vaginal ecosystem. In addition, the effectiveness of Lactobacillus as prophylaxis has also been well-founded in long-term administration. This review aimed to highlight the beneficial effects of lactobacilli derivatives (i.e. surface-active molecules) with anti-biofilm, antioxidant, pathogen-inhibition, and immunomodulation activities in developing remedies for vaginal infections. We also discuss the current challenges in the implementation of the use of lactobacilli derivatives in promotion of human health. In the current review, we intend to provide insights for the development of lactobacilli derivatives as a complementary or alternative medicine to conventional probiotic therapy in vaginal health.

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Section: Peptidoglycan (Pg)mentioning

confidence: 99%

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

2020

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“…For example, some candidate may induce activation of PRR (pattern recognition receptors)-mediated signaling pathways. Since Th1 responses contribute to clearance of infection and lead to protective memory response in a gonococcal mouse infection model [109][110][111], presence of a Th1 component may be advantageous for a tailored and robust anti-gonococcal immunity and could be exploited using different adjuvants (possibly mucosal). Sera cross-reactivity with different gonococcal strains suggested presence of heterologous cross-reactive epitopes.…”

Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection

et al. 2019

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There is an increasingly severe trend of antibiotic-resistant Neisseria gonorrhoeae strains worldwide and new therapeutic strategies are needed against this sexually-transmitted pathogen. Despite the urgency, progress towards a gonococcal vaccine has been slowed by a scarcity of suitable antigens, lack of correlates of protection in humans and limited animal models of infection. N. gonorrhoeae gene expression levels in the natural human host does not reflect expression in vitro, further complicating in vitro-basedvaccine analysis platforms. We designed a novel candidate antigen selection strategy (CASS), based on a reverse vaccinology-like approach coupled with bioinformatics. We utilized the CASS to mine gonococcal proteins expressed during human mucosal infection, reported in our previous studies, and focused on a large pool of hypothetical proteins as an untapped source of potential new antigens. Via two discovery and analysis phases (DAP), we identified 36 targets predicted to be immunogenic, membrane-associated proteins conserved in N. gonorrhoeae and suitable for recombinant expression. Six initial candidates were produced and used to immunize mice. Characterization of the immune responses indicated cross-reactive antibodies and serum bactericidal activity against different N. gonorrhoeae strains. These results support the CASS as a tool for the discovery of new vaccine candidates.

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“…These alternatives are mainly focused on the prevention of recurring infections rather than on the treatment of the disease. In this regard, early in vivo studies have been performed regarding the intravaginal administration of interleukin-12 (IL-12) in mice [ 36 ]. The study concludes that intravaginally administered IL-12 promotes the Th1-driven adaptive immune response, including the production of specific anti-gonococcal antibodies which would prevent recurring infection.…”

Section: Future Perspectivesmentioning

confidence: 99%

Future Prospects for Neisseria gonorrhoeae Treatment

Suay-García

Pérez‐Gracia

2018

Antibiotics

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Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the World Health Organization (WHO) Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis, and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting of dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. The increase in the detection of resistant gonococci may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics; (2) development of new antibiotics; and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this superbug. This has led the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

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Intravaginal Administration of Interleukin 12 during Genital Gonococcal Infection in Mice Induces Immunity to Heterologous Strains of Neisseria gonorrhoeae

Cited by 33 publications

References 38 publications

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection

Future Prospects for Neisseria gonorrhoeae Treatment

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