Vaccination against gonorrhea is high on the wish list of many experts. But the germs don’t make it easy for the researchers. Could a new intranasal vaccine bring about the gonococcal turnaround?
Effective vaccine protection against gonococci? Would be nice. In principle, the disease is a highly interesting candidate for vaccination. Neisseria gonorrhoeae is a true human pathogen that is practically non-existent in animals. And it causes more than just a bit of a burden of disease: it is estimated that between 80 and 90 million people worldwide contract it every year Tripper, the third most common sexually transmitted disease. In the EU it is (according to the Chlamydia infections) even the second most common. In Germany, gonorrhea in Saxony is notifiable. The reporting incidence there is currently around 20 per 100,000.
Compared to about the Syphilis Gonorrhea is a comparatively benign disease. Long-term complications are not known. Treatment is antibiotics, but there have recently been repeated warnings: Depending on the region, there are sometimes considerable problems with resistance, including to Fluorochinolone and against broad spectrumCephalosporins.
When research depressed
So why not just vaccinate away? If only it were that easy. The history of gonococcal vaccine research is rather depressing. The quadrivalent meningococcal B vaccine offers some protection in April 2022 showed. But here we are only talking about a risk reduction of one third. Otherwise: Bankruptcies as far as the eye can see. It all started in Alaska in the 1970s, where a dead cell vaccine in a small clinical study yielded absolutely nothing.
As a result, a vaccine was developed at great expense that protects against the Related of the gonococci, specifically against the protein pilin. The vaccine elicited an antibody response against gonococcal strains that contained the same pilin that was vaccinated against. However, it turned out that Pilin is genetically enormously variable. In clinical studies, the vaccination had no effect. Attempts to develop vaccinations directed against the most important protein in the outer gonococcal membrane, porin, have so far not had the hoped-for success.
Do gonococci have an immunosuppressive effect?
In addition to the genetic variability of the surface proteins, there is still other factors, making it difficult to develop vaccines against gonococci. On the one hand, the expression of some surface antigens – in addition to porin and pilin, these are also lipooligosaccharides (LOS) and the opacity protein (OPA) – is very variable. The respective proteins are also partially recombined prior to expression in a manner that is difficult to predict.
In addition, the immunity that the body develops against gonococci is not very strong even after an infection has been experienced. And this may not only be due to the variability of surface antigens, but also because gonococci actively suppress certain T-cell responses that are necessary for the establishment of sustained immunity.
From intravaginal to nasal
A new vaccine technique, which is still being explored in preclinical models, could solve some of the problems that have prevented gonococcal vaccines. The innovative vaccine company Intravacc has developed a gonococcal vaccine that is absorbed through the mucous membrane and in a current preclinical study achieved complete protection against gonococcal infections in animal models. The US health authority NIH or its sub-organization NIAID is at least impressed enough by the results to support the further development of the vaccine candidate with almost 15 million US dollars.
The vaccine – trade name Avacc 11® – was originally developed in an intravaginal application form. The current publication has now examined a nasal formulation – among other things with the (understandable) reason that men should also benefit from it. So-called Outer Membrane Vesicle, OMV for short. These contain most of the gonococcal-typical surface antigens in their natural form, i.e. not denatured by heat or chemically inactivated. This antigenic diversity is intended to counteract the problem of variability in gonococci.
No outliers so far
The second special feature is another “set” of vesicles that are also applied, namely microspheres, in which Interleukin-12 (IL-12) is encapsulated. The US vaccine developers were able to show that IL-12 has a pro-inflammatory effect and induces a Th1-controlled, cellular immune response. This had for vaginal application in the disease model, with simultaneous exposure to gonococci, the effect was that the infection was eliminated quickly and there was then immunity against reinfection.
The IL-12 microspheres were used as an adjuvant for the intranasal vaccine now being investigated. And that was very effective in the mouse model, as the researchers wrote in their journal mSphere report work published by the American Society of Microbiology. The mice, both males and females, developed sufficiently high serumIgG-titers, and also IgA was detectable in the saliva. In the female mice, both IgG and IgA were found in the vaginal mucosa in concentrations similar to those achieved with vaginal application. And increased in the iliac lymph nodes produced CD4 T cells after vaccination Gamma-Interferonalso to a similar extent regardless of the route of application.
The great advantage of vaccination with OMV plus IL-12 is that the resulting immunity is not specific for certain gonococcal strains, emphasize the authors working with Prof. Michael Russell from the University of Buffalo. On the contrary, so far they have not found a strain that would not have been detected by the induced antibodies. It could therefore be that a vaccination against gonococci has to cover a sufficiently broad spectrum of antigens in order to work. This is now to be further investigated before the first clinical studies can begin.
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