User:CRRodriguez/Letter to Strathmann

Dear Dr. Peschel,

I have been extremely happy to learn that Gynatren is once again available. This time I am writing to you on another matter, and I would like to please direct your attention to an interesting question I just noticed. You may already be well aware of this problematic, but let me just briefly make my point anyway.

As you surely already know, Lactobacillus iners, a frequently found species of vaginal microbiota, has been associated with poor reproductive health. To me it seems, there are some similarities between L. iners and the lactobacilli in your vaccine, namely:


 * 1) L. iners is often the dominant lactobacillus species after metronidazole treatment. a The strains in your vaccine have been isolated in trichomoniasis from microbial communities probably also exposed to metronidazole.
 * 2) L. iners strains found in disease show coccobacillary morphology. b The same has been noted about the vaccine strains.
 * 3) L. iners is suspected to be a pathosymbiont of Gardnerella vaginalis. The vaccine strains have been hypothesized to be pathosymbionts of Trichomonas vaginalis.
 * 4) L. iners produces a pore-forming cytolytic toxin (inerolysin), possibly laterally acquired from G. vaginalis. There have been discussions about the vaccine strains also producing a cytotoxin. The possibility of a lateral relationship with T. vaginalis has been discussed.
 * 5) Lack of H2O2 production. c

There have been some recent efforts to selectively suppress L. iners and promote L. crispatus and other favorable species in women treated with metronidazole in order to reduce relapse rates. One such approach was the oral and intravaginal administration of lactoferrin with the purpose of binding free iron, which is required by L. iners, but not by other lactobacillus species. Another experimental in vitro approach is the usage of cysteine uptake inhibitors. As it turns out, L. iners but not other lactobacilli, requires monomeric cysteine for its growth, which can be made unavailable in this way. Yet another approach utilizes bacteriocins other lactobacilli produce to outcompete L. iners, which is clearly selective in nature. None of the proposed approaches to my knowledge involves immunization against L. iners. I assume researchers are wary of the danger of indiscriminately harming gastrointestinal and urogenital lactobacillus communities in a cross-reactive manner. We know from Gynatren, that that does not have to necessarily be the case.

The research field really is buzzing compared to just five years ago. The modulation of vaginal lactobacilli composition seems to be finally recognized as an important therapeutic target. Masson et al. as recently as March of this year called for “reconceptualizing BV treatment” in Nature : BV should be viewed as cured only if the vaginal epithelium is repopulated with lactobacillus strains that are actually capable to fend off pathogens. I think the time right now is as adequate as it ever will be to bring your knowledge back into the discussion.

I find it an intriguing possibility, that the vaccine strains may be antigenically related with L. iners. The species in the vaccine, L. rhamnosus, L. vaginalis, L. fermentum and L. salivarius are normally less abundant in women, both in health and under BV conditions. The action against strains of these species thus seems to be an insufficient explanation of vaccine efficacy. However, if an immunological cross-reaction with L. iners were to be found, this would explain why 65-70% of women benefit from vaccination, which is much more than the percentage that actually harbors the vaccine species in abundant quantities. This would be a revolutionary discovery that would surely widen the recognition of Gynatren.

There has been much progress in microbiology and immunology since the last published efforts to understand and explain lactobacillus vaccines. Based on recent developments, I think it would be worthwhile to examine the possible influence of vaccine-induced immunity on L. iners colonization. If vaccine-induced antibodies were directly reactive with L. iners but not with L. crispatus, that would be a huge win. But even if an indirect modulation favoring L. crispatus or L. jensenii as opposed to L. iners or L. gasseri were to be found, this would be really helpful. It could change the narrative from "LV promotes normal lactobacilli and inhibits aberrant lactobacilli" to "it promotes L. crispatus and inhibits L. iners", or something to a similar effect. It would clarify the mechanism of action in a way that people are willing to accept. And if the truth is even more complex, and this simple idea cannot be the final answer to how the vaccine really works, the investigation would still bring us at least one small step closer.

I apologize for the unsolicited advice. Thank you very much for considering. I wish you the best of luck and much success relaunching your vaccine.

Best regards, Anna Kupfer

P.S.: I am a Hungarian-born medical physicist and Wikipedia-editor, and I sometimes promote lactobacillus vaccines on the Internet in my spare time, because of how much they have helped me.

At the 1957 congress in Reims [1], the transmission mechanisms of trichomoniasis in man were discussed and infection by sexual intercourse was proven. Although the problem appeared to have been solved at that time, many gynaecologists and venereologists were slow to accept this thesis.

The venereologists had already recognized trichomoniasis as a venereal disease in men. This is because trichomonads had been found in the vagina of the sexual partners of men with urethritis of this aetiology. The reverse mechanism, however, i.e., that women could be infected by men suffering from trichomoniasis, which is usually symptomless in men, was not accepted.

The veterinary surgeons already knew in those days that an infected bull could infect the cows which he serviced (artificial insemination of cows was not yet extensively practised), leading finally to endometritis and repeated abortions.

At the 1957 congress in Reims [1], the transmission mechanisms of trichomoniasis in man were discussed and infection by sexual intercourse was proven. Although the problem appeared to have been solved at that time, many gynaecologists and venereologists were slow to accept this thesis.

The venereologists had already recognized trichomoniasis as a venereal disease in men. This is because trichomonads had been found in the vagina of the sexual partners of men with urethritis of this aetiology. The reverse mechanism, however, i.e., that women could be infected by men suffering from trichomoniasis, which is usually symptomless in men, was not accepted.

The veterinary surgeons already knew in those days that an infected bull could infect the cows which he serviced (artificial insemination of cows was not yet extensively practised), leading finally to endometritis and repeated abortions.