Human Testing. Several animal models have been attempted, but none has been satisfactory, and this has impeded vaccine development. Because of this, however, researchers have learned a great deal about the genetics, molecular biology, and pathophysiology of the organism—how it works and how it evades the immune response. Many researchers have now decided that the time has come to move to human subjects, the only relevant model, in order to develop a vaccine in an intelligent, rational, and cost-effective manner.
One group has challenged over 80 male human experimental volunteers with gonococci in the past few years, establishing several important points. First of all, it is safe. Second, several proteins appear to be sufficient or facilitative for infection, but no single protein appears to be truly necessary or essential for infection. Third, the core polysaccharides of LOS do appear to be absolutely essential to infection, which is another argument for including antibodies to these surface molecules in a vaccine.
In response to questions from the audience, Dr. Sparling added the following:
It is possible that there will be Phase I and Phase II trials in the next few years, at least on the pilus- and Por-based vaccines. If these trials don’t go well, it will take additional years to develop the information needed to go forward with the other candidate antigens described above.
Progress is a factor of people and money. The field has been moving relatively slowly because there has been little focus on gonococcus vaccine per se.
The LOS antigen could be developed as an anti-idiotypic vaccine, but it wouldn’t have to be. Another possibility would be to combine that core sugar with another antigen in a complex protein-carbohydrate vaccine.
The LOS antigen has not yet been tested in humans. It does give a good booster response (IgA and IgM) in mice and rabbits, but this is only a surrogate for opsonic and bacteriocidal activity.
Work on the other antigens—Tbp1, Tbp2, and FrpB—is still at an early stage of concept development.
It would be desirable to administer the vaccine orally or intranasally. Shigella might be an attractive vector, but there are other potential vectors, as well as cytokines, to target the vaccine.
The target population would be, at the least, young people as soon as they’ve had their first incident of any sexually transmitted disease.