Candida vaginitis: virulence, host response and vaccine prospects

Abstract

Vulvovaginal candidiasis is a common mucosal infection affecting a large proportion of women with some of them affected by recurrent often intractable forms of the disease. Thus, there is an increasing interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in animal models of vaginal candidiasis, the components of the host-fungus interaction at the mucosal level.The evidence of an immune response in the vaginal compartment was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Aspartyl-proteinase (Sap2), which is an important immunodominant antigens and virulence factors of C.albicans acting in mucosal infections, was assembled with virosomes and a vaccine PEV7 was obtained. The results obtained in the mouse model and in the clinical trial conducted by Pevion on women have evidenced that the vaccine PEV7, intravaginally administered, has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. This opens the way to a modality for anti-Candida protection at mucosal level.

Fungal-Bacterial Interactions in Health and Disease

“…About 75% of women suffer at least one episode of VVC in their life [161]. The main pathogen causing VVC in these women is the species C. albicans , followed by C. glabrata , C. tropicalis , and C. parapsilosis [161,162]. In addition to hormone replacement, pregnancy, immunosuppression, habits of hygiene, and other risk factors, the elimination of protective bacteria by antibiotic treatment also increases the risk for VVC [163].…”

Nanoparticle-based vaccines

“…For Candida albicans that can cause vulvovaginal mucosal infections, Pevion used the aspartyl-proteinase (Sap2), which is an immunodominant antigen and virulence factor; this recombinant protein was assembled with virosomes (PEV7). The evaluation in mouse model and the initial clinical trial on women showed that this candidate vaccine, intravaginally administered, has a therapeutic potential for the treatment of recurrent candidiasis [42]. In addition, this company tested a malaria vaccine in Africa.…”

Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response

“…PEV7 was developed by Pevion Biotech (rights subsequently acquired by NovaDigm Therapeutics) and contains recombinant secreted aspartyl protease 2 (rSAP-2) incorporated into influenza virisomes. Trial results demonstrated the generation of specific and functional B cell memory in 100% of the vaccinated women and a favourable safety profile (388). Earlier reports of an oral vaccine, D.651, for the prevention of VVC recurrence was prepared using ribosomes of C. albicans serotypes a and b.…”

“…In another study, a vaccine consisting of formaldehyde-killed spherules of Coccidioides immitis was tested in humans, but a statistically significant reduction of the incidence of infection was not observed in those vaccinated ( 390 ). A number of other fungal vaccines have been tested in animal models and are beyond the scope of this manuscript, but have been the subject of several recent reviews ( 328 , 383 , 388 , 391 – 394 ). The vaccines described above represent the only ones to reach clinical trials to the best of the authors knowledge.…”