Neisseria gonorrhoeae Vaccines
Widespread spread of gonorrhea and the emergence of the drug-resistant Neisseria gonorrhoeae strain has made the development of the Neisseria gonorrhoeae vaccine a global concern. Creative Biolabs has many years of research experience in gonorrhea vaccines. Under the leadership of the top scientists' team, we have conducted a lot of in-depth research on the antigenic variation, pathogenic mechanism, immune response of N. gonorrhoeae, and made gratifying achievements in animal models of gonorrhea. Therefore, we are confident enough to provide you with reliable products and services related to the N. gonorrhoeae vaccine.
Neisseria gonorrhoeae
Neisseria gonorrhoeae, also known as gonococcus, is a gram-negative diplococcus and the causative agent of the sexually transmitted disease gonorrhoea. The bacteria are mainly colonized in the genital mucosa and are also distributed in the nasopharynx and eyes. N. gonorrhoeae damages the host by activating the innate immune response of its colonization site. Inadequate treatment of N. gonorrhoeae in women may lead to genital tract infections including infertility, ectopic pregnancy, and pelvic inflammatory disease, and infections during production may cause blindness in newborns. In addition, N. gonorrhoeae may also lead to an increase in the incidence of infectious arthritis and endocarditis if it is left untreated and develops into disseminated gonorrhea infection. N. gonorrhoeae can only be transmitted through sex, including through the oral, vaginal, and anal sex. It was thought that the bacteria spread by attaching to sperm, but this hypothesis cannot explain the fact that gonorrhea can spread from women to men. The new findings speculate that the bacteria are anchored to the proteins on the sperm by the pili and move through the coital liquid.
Pathogenicity of Neisseria gonorrhoeae
N. gonorrhoeae adheres to the epithelial cells in the mucosa through the surface structure of the Opa proteins, LOS, type IV pili, and PorB (major outer membrane protein porin). Among them, type IV is the decisive factor for bacterial attachment and colonization on the surface of epithelial cells. It is also the key to bacterial twitching movement, initiating cell adhesion, exerting natural transformational ability, and evading the body's immune response. The interaction of Opa proteins with CEACAM receptors and molecules such as heparin sulfate is also important for bacterial adhesion to cells. N. gonorrhoeae is highly adaptable to the human body to ensure its survival and replication. This is achieved by transcriptional regulation through regulatory sRNAs and by variation through phase variation. Long-term evolution and adaptation have enabled N. gonorrhoeae to encode sRNAs, two-component systems, and 34 possible specialized transcriptional regulators. For example, transcriptional regulators such as MtrR, MtrA, and MpeR regulate the efflux pump MtrC-MtrD-MtrE, which is responsible for the export of antimicrobial peptides, while RpoH (RNA polymerase-σ factor) can maintain protein homeostasis, and the two-component system MisR-MisS can respond and adjust to membrane stress.
Fig.1 Overview of N. gonorrhoeae pathogenesis factors.
N. gonorrhoeae adapts to the host by evading the recognition and attack of the human complement system. The bacterium's escape from complement-mediated killing is through 1) binding and inactivating the complement cascade component and preventing the formation of membrane attack complexes; 2) expressing host molecules on its surface and binding to complement regulatory proteins (Quillin SJ and Seifert HS, 2018). Because N. gonorrhoeae is very sensitive to the complement composition of animals, the evasion ability of the bacteria for complement recognition and killing is an important reason for its effective colonization and growth. During infection, N. gonorrhoeae is able to modulate the activation state of dendritic cells and survive in macrophages and neutrophils. This bacterium can still survive and regulate the production of inflammatory cytokines and regulate apoptosis in macrophages. In addition, N. gonorrhoeae is also capable of polarizing macrophages and causing them to fail to activate T cells. Similarly, the ability of DCs exposed to the bacteria to stimulate T cell proliferation is also greatly reduced. Most importantly, N. gonorrhoeae is able to alter the antigenic structure of type IV pili, LOS, and opacity (Opa) proteins on its surface, and therefore cannot produce immune memory. Moreover, N. gonorrhoeae can also inhibit the proliferation and activation of Th1 and Th2 cells by affecting the production of cytokines, thereby regulating the adaptive immune response.
Development of the Neisseria gonorrhoeae Vaccines
With the advent of more and more antibiotic-resistant N. gonorrhoeae strains, the preparation of vaccines that prevent gonorrhea has become an urgent issue. Since N. gonorrhoeae can change the antigenic structure of its surface components, the host can hardly produce immunological memory for the bacteria, thus hindering the development of the N. gonorrhoeae vaccine. In addition, the lack of understanding of protective immunity and the absence of effective animal models also make the development of N. gonorrhoeae vaccines challenging. In the past, whole-cell, pili-based, partially autolyzed, and protein I-based vaccines entered the clinical phase, but the results showed that none of these four vaccines had protective effects. A recent study found that the incidence of gonorrhea was significantly lower in patients vaccinated with an OMV-based vaccine against serogroup B Neisseria meningitidis. The protective effect of the vaccine on gonorrhea was observed during and after the vaccination. Although the effective rate was only 31%, this level of protection is able to reduce the rate of prevalence of the current 1.6-1.7% of the disease by almost half within 15 years. Therefore, the use of serogroup B meningococcal vaccine to prevent gonorrhea has also become one of the strategies for developing N. gonorrhoeae vaccine. The N. gonorrhoeae antigens that are currently under investigation as vaccine candidates include the outer membrane porin, PorB, phospholipase D (PLD), MtrE of the Mtr efflux pump complex, nitrite reductase, AniA, transferrin-binding proteins, TbpAB, the methionine uptake receptor, MetQ, and some outer membrane proteins.
Our Services in N. gonorrhoeae Vaccine Development
- Screening and identification of bacterial conserved antigens
- Determination of immunization routes and schemes
- Design of appropriate vaccine formulation and delivery system
- Establishments of various kinds of animal models
- Small- and large-scale production of the vaccine
- Preclinical evaluation of the vaccine candidate
After years of unremitting efforts and consistent service spirit, Creative Biolabs has become a rising star in the vaccine industry. Our expertise in vaccine research has helped clients around the world complete their vaccine development perfectly and efficiently, winning the unanimous approval of all researchers. If you have any needs, please contact us immediately, we will provide you with the best products and services!
Reference
- Quillin SJ, Seifert HS. (2018). “Neisseria gonorrhoeae host adaptation and pathogenesis”. Nat Rev Microbiol. 16(4), 226-240.
All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.
