of vaccine efficacy. humoral immune response serum anti-aberrant-lactobacillus antibody titres (geometric mean and standard error) in 97 women vaccinated with solcotrichovac (milovanović 1983). a booster dose was given 12 months after the first injection. total secretory iga concentration (arithmetic mean and standard error) of the vaginal secretions of 95 women vaccinated with solcotrichovac (rüttgers 1988). mucosal surfaces are a major portal of entry for pathogens into the body. antibodies in mucosal secretions represent the first line of immune defense of the mucosae. they are capable to bind to specific pathogens and prevent their adherence to the epithelial cell lining of the mucous membranes. neutralized pathogens can then be eliminated from the mucosal surfaces by means of conveyance by the mucus stream. mucosae throughout the body have been described as parts of a common mucosal immune system (cmis). the basis for this concept is the observation that precursor lymphocytes sensitized to a certain antigen at a specific mucosal site can migrate and assume effector function at distant mucosal tissues. although the female genital tract is thought of as part of the cmis, it shows some characteristics that set it apart from other mucosal immune sites. one of these features is the relative inefficacy of local antigenic stimulation owing to a sparsity of mucosal lymphoepithelial inductive sites. a further distinctive characteristic is the significant contribution of the systemic immune compartment to the pool of antibodies. in most external secretions, like tears, saliva or milk, the dominant antibody class is secretory iga (siga), whereas in the cervicovaginal secretions igg levels equal or exceed the levels of siga. a large portion of this igg is thought to originate from the circulation and appear in vaginal fluids via transudation through the uterine tissues. there are reports that systemic immunization can stimulate humoral immune protection in vaginal secretions more efficiently than in other mucosal secretions, where serum-derived igg concentrations remain lower. milovanović and coworkers studied the serum antibody response of 97 women with trichomonad colpitis to primary immunization with solcotrichovac (3 intramuscular injections of 0.5 ml vaccine at intervals of 2 weeks) and a booster dose of 0.5 ml administered 12 months after the first injection. the agglutination titres were determined by preparing two-fold serial dilutions of the serum samples in isotonic saline (dilutions of 1:10 to 1:1280), using 0.5 ml concentrated lactobacillus vaccine as an agglutinogen. an at least threefold elevation of the agglutination titres following primary immunization was detected in the serum of 93.8% of patients; the rest of the patients were considered non-responders or poor responders to the vaccination. the geometric mean of the agglutination titres increased from the basal level of 1:56 before vaccination to 1:320 after finishing the primary immunization program, and it was still 1:140 one year later. two weeks after the booster injection the mean titres were raised back to 1:343. rüttgers quantified the total concentration of secretory iga antibodies in the vaginal secretions of 192 women with bacterial vaginitis participating in a randomized, double-blind, placebo-controlled study. 95 patients were treated with solcotrichovac and 97 with placebo, according to the primary immunization scheme described above. the samples were tested using the enzyme‐linked immunosorbent assay according to åkerlund et al. the mean baseline concentrations were similar in the two comparative groups. one month after the start of the therapy the siga concentration in the active-treatment group had risen significantly compared to the baseline and also in comparison to the placebo group. this difference gradually decreased over the subsequent months. after 12 months the siga concentration in the solcotrichovac group had fallen back to baseline value. about 35% of the actively treated patients had not developed a pronounced mucosal immune response. in these patients siga concentration of the vaginal secretion remained unchanged or showed only a short-lived elevation. rüttgers observed that this group of patients by large overlapped with those, that had had reinfections during the follow-up period of 12 months, and concluded that vaginal siga concentration is a better correlate to immune protection than serum antibody titres. on the question of the mechanism underlying the induction of iga-secreting plasma cells in the vaginal mucosa, pavić and stojković suggested that intramuscularly administered antigens may be transported to the local immunocompetent organ, in this case the vagina, and provoke a local secretory immune response. patrolling dendritic cells exposed to killed bacterial antigens at a muscular injection site however typically do not migrate further than the local draining lymph nodes, where antigen presentation and the activation of t and b cells occur. effector and memory lymphocytes in turn preferentially home back to the tissue where they were first activated, in this case the secondary lymph nodes. this is the reason why parenteral immunization with non-replicating antigens is generally considered ineffective in eliciting a mucosal immune response. another possible explanation for an increased level of anti-aberrant-lactobacillus siga in vaginal secretions involves natural priming by mucosal infection at this site. similarly to how subcutaneously administered killed whole-cell cholera vaccines reportedly only provoke substantial mucosal secretory antibody response in cholera‐endemic countries, vaginal priming with aberrant lactobacilli may be necessary for the generation of mucosal iga-secreting plasma cells following parenteral vaccination. effect on the vaginal ecology protective lactobacilli inhibit the growth of other microorganisms by competing for adherence to epithelial cells and by producing antimicrobial compounds. these compounds include lactic acid, which lowers the vaginal ph, hydrogen peroxide and bacteriocins. aberrant strains of lactobacilli are incapable to effectively control the vaginal microbiota, leading to an overgrowth of a mixed flora of aerobic, anaerobic and microaerophilic bacterial species. antibodies and cellular defense mechanisms directed against aberrant lactobacilli induced by vaccination have been shown to change the composition of the vaginal flora. milovanović and his coworkers found a marked reduction in prevalence of klebsiella and proteus infestations in 36 trichomoniasis patients under therapy with solcotrichovac, while normal, metabolically active lactobacillus species that could initially be found in only 11% of patients, were present in 72% after finishing treatment. karkut observed a significant reduction in the incidence of escherichia coli (55% to 23%), group b streptococci (37% to 10%), enterococci (36% to 12%), bacteroides (25% to 3%) and gardnerella vaginalis (37% to 9%) in 94 patients treated for recurrent bacterial vaginitis eight weeks after initial injection. the incidence of aberrant lactobacilli fell from 17% to 3%, while that of normal lactobacilli rose from 31% to 72% during the course of the eight weeks. harris reported a significant reduction of the number of microbial species (other than lactobacilli) found in post-treatment cultures from 77 patients. litschgi found, that the incidence of mixed bacterial infections characterized by the presence of g. vaginalis, haemolytic streptococci and staphylococci was reduced by two-thirds four weeks after finishing therapy in 120 patients treated for bacterial colpitis. he observed a similar reduction of the less frequent klebsiella, proteus-dominant infections. a quantitative bacteriological analysis has been performed by milovanović and coworkers in a group of 36 trichomoniasis patients. the study aimed at quantifying locally unusual and mostly pathogenic organisms, whereby anaerobes were excluded for methodological reasons. bacterial counts of aerobes excluding lactobacilli reportedly dropped from 18,900 organisms per 0.1 ml vaginal secretion on the day of the first solcotrichovac injection to 5800 organisms 112 days thereafter. goisis and his coworkers reported a mean count of lactobacilli of 1.6×106 organisms per ml vaginal secretion before vaccination with solcotrichovac in 19 trichomoniasis patients. one month after the start of the treatment the count increased to 4.6×106 bacilli per ml. in 46 patients with bacterial vaginitis the lactobacillus counts were significantly higher during the entire course of treatment with 8.6×106 bacilli per ml before and 15×106 bacilli per ml after vaccination. while this study summed the counts of normal and aberrant lactobacilli, microscopic study of the fixed, gram-stained smears of vaginal secretions revealed lactobacilli of differing lengths, with a predominance of short forms in trichomoniasis patients before vaccination; the bacilli retained this tendency even in cultures started from the secretion samples. the morphology of lactobacilli shifted towards normal rod-shaped forms under therapy in most patients, which property was once again retained in culture. müller and salzer have confirmed the quantitative increase in physiological lactobacilli under vaccination therapy of 28 patients with recurrent bacterial infections. the decreasingly diverse and numerous populations of non-lactic acid-producing bacteria and the concurrent growth of normal, metabolically active lactobacilli lead to a gradual decrease of vaginal ph. goisis and his coworkers reported in trichomoniasis patients a mean ph value of 6.14 at the time of the first injection, 5.64 two weeks later, and 5.23 on the day of treatment completion, two weeks after the second visit. in patients with vaginitis not caused by trichomonads a mean initial ph of 5.81 was documented, which dropped to 5.39 two weeks later and finally to 4.98. karkut has published very similar results. boos and rüttgers measured in 182 patients with bacterial vaginitis a vaginal ph of 4.90 before therapy and 4.26 six months after the start of therapy. history invention in 1969 a research project was started in budapest, hungary to develop a vaccine against trichomoniasis, initiated by györgy philipp, a hungarian gynaecologist and led by károly újhelyi, head of the vaccine production and research department of the hungarian institute of public health, one of the most distinguished hungarian physician-scientists of the 20th century and a pioneer of vaccine research and technology. in 1972 the research group reported vaccinating 300 patients with acute trichomonal colpitis with autovaccines consisting primarily of inactivated trichomonas vaginalis strains cultured from vaginal samples of the patients themselves, along with some residual amounts of the accompanying bacterial flora, inadvertently present in the cultures. despite of a marked alleviation of clinical symptoms, all trichomoniasis patients still tested positive upon completion of the autovaccine therapy. újhelyi and his coworkers attributed the partial therapeutic effect to the bacterial residue in the t. vaginalis cultures used for the vaccine. they identified a gram-positive lactobacillus with a tendency to polymorphism commonly present in the accompanying flora of trichomoniasis patients. to test their assumption, further 700 patients each received treatment with an inactivated bacterial vaccine composed of one of 16 such polymorphic lactobacillus strains. the effect was studied on eight patient groups with the following conditions: (1) colpitis, including trichomonal colpitis (2) erythroplakia (3) endocervicitis (4) upper genital tract infection (5) urinary tract infection (6) infertility (7) genital lesions and tumors (8) trichomoniasis during pregnancy, childbirth and postpartum period. treatment with the experimental bacterial vaccines was capable to eliminate trichomoniasis in 28% of infected patients and resolved or alleviated many of the examined urogenital conditions. after this initial breakthrough, újhelyi and his coworkers directed their efforts into the development and optimization of gynevac, a composite bacterial vaccine, containing five aberrant, polymorphic lactobacillus strains. erika lázár, a hungarian gynaecologist and specialist in the field of reproductive medicine, and her coworkers performed many of the clinical trials on gynevac, focusing clinical and research interest on the prevention of ascending infections during pregnancy. in two prospective studies performed between 1976 and 1982 in rural, socioeconomically disadvantaged kazincbarcika with the enrollment of nearly 3500 pregnant women, lactobacillus vaccination appeared to reduce the incidence of preterm birth by about 40%. 1980-2012 in 1975 the research group of újhelyi sold the unpatented technology to solco basel ag, a swiss pharmaceutical company with the agreement, that solco would manufacture and market the vaccine in western europe, whereas the hungarian company humán oltóanyagtermelő vállalat (later vakcina kft.) would supply the eastern markets ("soviet bloc"). in 1980 solco's researchers patented the vaccine; in 1981 the company obtained regulatory approval and started marketing the vaccine under the trade name solcotrichovac. after prolonged clinical trials, mainly driven by lázár, the production and marketing of gynevac started in hungary in 1997. after solco's acquisition of the technology, mainly swiss and german researchers have joined the investigations. in 1980 mario litschgi reported a cure rate of trichomoniasis of 92.5% in a clinical study with 427 female participants. following this initial success, a number of studies have been conducted on the vaccine. most of the reports can be found in the proceedings of two symposia: the symposium on trichomoniasis (1981) featured investigations with trichomonas vaginalis-infected women and mainly clinical results, whereas the symposia on the immunotherapy of vaginal infections (1983) focused on the therapy of bacterial infections and delved into the mechanism of action.