A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis—A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial
Open accessAbstract
Background: Recurrent vulvovaginal candidiasis (RVVC) is a problematic form of mucosal Candida infection, characterized by repeated episodes per year. Candida albicans is the most common cause of RVVC. Currently, there are no immunotherapeutic treatments for RVVC. Methods: This exploratory randomized, double-blind, placebo-controlled trial evaluated an immunotherapeutic vaccine (NDV-3A) containing a recombinant C. albicans adhesin/invasin protein for prevention of RVVC. Results: The study in 188 women with RVVC (n = 178 evaluable) showed that 1 intramuscular dose of NDV-3A was safe and generated rapid and robust B- and T-cell immune responses. Post hoc exploratory analyses revealed a statistically significant increase in the percentage of symptom-free patients at 12 months after vaccination (42% vaccinated vs 22% placebo; P = .03) and a doubling in median time to first symptomatic episode (210 days vaccinated vs 105 days placebo) for the subset of patients aged <40 years (n = 137). The analysis of evaluable patients, which combined patients aged <40 years (77%) and ≥40 years (23%), trended toward a positive impact of NDV-3A versus placebo (P = .099). Conclusions: In this unprecedented study of the effectiveness of a fungal vaccine in humans, NDV-3A administered to women with RVVC was safe and highly immunogenic and reduced the frequency of symptomatic episodes of vulvovaginal candidiasis for up to 12 months in women aged <40 years. These results support further development of NDV-3A vaccine and provide guidance for meaningful clinical endpoints for immunotherapeutic management of RVVC. Clinical Trials Registration: NCT01926028.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In C. albicans, targeting adhesin proteins with vaccines decreases adhesion to and biofilm formation on plastic surfaces, invasion of vaginal epithelial cells, and virulence.
“In the model fungal pathogen C. albicans, targeting adhesin proteins with vaccines results in a decrease in adhesion to and biofilm formation on plastic surfaces, including catheters, invasion of vaginal epithelial cells, and virulence22–24.”
From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [24]
The paper describes NDV-3A as targeting Als3, an adhesin/invasin and virulence factor, and reports fewer symptomatic vaginal candidiasis recurrences after vaccination in women under 40 (Introduction and Results; page numbers unavailable). It does not report that vaccination decreased adhesion or biofilm formation on plastic or catheters, invasion of vaginal epithelial cells, or fungal virulence directly. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hidden Killers: Human Fungal Infections
Brown, G. D., Denning, D. W., Gow, N. A. R., Levitz, S. M., Netea, M. G., & White, T. C. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004404 · Cited by 4,284 · see citing works
The Diagnosis of Strep Throat in Adults in the Emergency Room
Centor, R. M., Witherspoon, J. M., Dalton, H. P., Brody, C. E., & Link, K. (1981) · Medical Decision Making · doi:10.1177/0272989x8100100304 · Cited by 761 · see citing works
Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells
Phan, Q. T., Myers, C. L., Fu, Y., Sheppard, D. C., Yeaman, M. R., Welch, W. H., Ibrahim, A. S., Edwards, J. E., & Filler, S. G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050064 · Cited by 641 · see citing works
Self-citationRecurrent vulvovaginal candidiasis
Sobel, J. D. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.06.067 · Cited by 502 · see citing works
Self-citationMaintenance Fluconazole Therapy for Recurrent Vulvovaginal Candidiasis
Sobel, J. D., Wiesenfeld, H. C., Martens, M., Danna, P., Hooton, T. M., Rompalo, A., Sperling, M., Livengood, C., Horowitz, B., Von Thron, J., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033114 · Cited by 487 · see citing works
Self-citationLin, L., Ibrahim, A., Xu, X., Farber, J., Avanesian, V., Baquir, B., Fu, Y., French, S., Edwards, J., & Spellberg, B. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000703 · Cited by 479 · see citing works
Self-citationFunctional and Structural Diversity in the Als Protein Family of Candida albicans
Sheppard, D. C., Yeaman, M. R., Welch, W. H., Phan, Q. T., Fu, Y., Ibrahim, A. S., Filler, S. G., Zhang, M., Waring, A. J., & Edwards, J. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401929200 · Cited by 300 · see citing works
Self-citationSchmidt, C. S., White, C. J., Ibrahim, A. S., Filler, S. G., Fu, Y., Yeaman, M. R., Edwards, J. E., & Hennessey, J. P. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.10.038 · Cited by 233 · see citing works
Self-citationFu, Y., Ibrahim, A. S., Sheppard, D. C., Chen, Y., French, S. W., Cutler, J. E., Filler, S. G., & Edwards, J. E. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02873.x · Cited by 218 · see citing works
Self-citationFluconazole-Resistant Candida albicans Vulvovaginitis
Marchaim, D., Lemanek, L., Bheemreddy, S., Kaye, K. S., & Sobel, J. D. (2012) · Obstetrics & Gynecology · doi:10.1097/aog.0b013e31827307b2 · Cited by 195 · see citing works
Self-citationSpellberg, B. J., Ibrahim, A. S., Avanesian, V., Fu, Y., Myers, C., Phan, Q. T., Filler, S. G., Yeaman, M. R., & Edwards, Jr. (2006) · The Journal of Infectious Diseases · doi:10.1086/504691 · Cited by 180 · see citing works
Self-citationAballéa, S., Guelfucci, F., Wagner, J., Khemiri, A., Dietz, J.-P., Sobel, J. D., & Toumi, M. (2013) · Health and Quality of Life Outcomes · doi:10.1186/1477-7525-11-169 · Cited by 126 · see citing works
Self-citationNDV-3 protects mice from vulvovaginal candidiasis through T- and B-cell immune response
Ibrahim, A. S., Luo, G., Gebremariam, T., Lee, H.-K., Schmidt, C. S., Hennessey, J. P., French, S. W., Yeaman, M. R., Filler, S. G., & Edwards, J. E. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.09.016 · Cited by 97 · see citing works
Self-citationIbrahim, A., Spellberg, B., Avanesian, V., Fu, Y., & Edwards, J. (2006) · Infection and Immunity · doi:10.1128/iai.74.5.3039-3041.2006 · Cited by 83 · see citing works
Self-citationIbrahim, A. S., Spellberg, B. J., Avenissian, V., Fu, Y., Filler, S. G., & Edwards, J. E. (2005) · Infection and Immunity · doi:10.1128/iai.73.2.999-1005.2005 · Cited by 83 · see citing works
Self-citationContribution of Candida albicans ALS1 to the Pathogenesis of Experimental Oropharyngeal Candidiasis
Kamai, Y., Kubota, M., Kamai, Y., Hosokawa, T., Fukuoka, T., & Filler, S. (2002) · Infection and Immunity · doi:10.1128/iai.70.9.5256-5258.2002 · Cited by 80 · see citing works
Self-citationFunctional analysis of the <i>Candida albicans ALS1</i> gene product
Loza, L., Fu, Y., Ibrahim, A. S., Sheppard, D. C., Filler, S. G., & Edwards, J. E. (2004) · Yeast · doi:10.1002/yea.1111 · Cited by 78 · see citing works
Self-citationSpellberg, B. J., Ibrahim, A. S., Avenissian, V., Filler, S. G., Myers, C. L., Fu, Y., & Edwards, J. E. (2005) · Infection and Immunity · doi:10.1128/iai.73.9.6191-6193.2005 · Cited by 78 · see citing works
Self-citationGene Overexpression/Suppression Analysis of Candidate Virulence Factors of Candida albicans
Fu, Y., Luo, G., Spellberg, B., Edwards, J., & Ibrahim, A. (2008) · Eukaryotic Cell · doi:10.1128/ec.00445-07 · Cited by 72 · see citing works
Self-citationSpellberg, B. J., Johnston, D. A., Phan, Q. T., Edwards, J. E., French, S. W., Ibrahim, A. S., & Filler, S. G. (2003) · Infection and Immunity · doi:10.1128/iai.71.10.5756-5764.2003 · Cited by 68 · see citing works
Self-citationFluconazole use and birth defects in the National Birth Defects Prevention Study
Howley, M. M., Carter, T. C., Browne, M. L., Romitti, P. A., Cunniff, C. M., & Druschel, C. M. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.11.022 · Cited by 54 · see citing works
Coleman, D. A., Oh, S.-H., Marretta, S. M., & Hoyer, L. L. (2011) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.2011.00914.x · Cited by 19 · see citing works
Patient and Parent-Reported Signs and Symptoms for Group A Streptococcal Pharyngitis
Lindgren, C., Neuman, M. I., Monuteaux, M. C., Mandl, K. D., & Fine, A. M. (2016) · PEDIATRICS · doi:10.1542/peds.2016-0317 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L., & Kullberg, B. J. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.26 · Cited by 1,636 · see citing works
Tackling the emerging threat of antifungal resistance to human health
Fisher, M. C., Alastruey-Izquierdo, A., Berman, J., Bicanic, T., Bignell, E. M., Bowyer, P., Bromley, M., Brüggemann, R., Garber, G., Cornely, O. A., et al. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00720-1 · Cited by 1,179 · see citing works
Antifungal Drug Resistance: Molecular Mechanisms in <i>Candida albicans</i> and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801 · see citing works
Guideline: Vulvovaginal Candidosis (AWMF 015/072, Level S2k)
Farr, A., Effendy, I., Frey Tirri, B., Hof, H., Mayser, P., Petricevic, L., Ruhnke, M., Schaller, M., Schaefer, A. P. A., Sustr, V., et al. (2021) · Mycoses · doi:10.1111/myc.13248 · Cited by 184 · see citing works
Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species
Sobel, J. D., & Sobel, R. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1476490 · Cited by 168 · see citing works
Self-citationNyirjesy, P., Brookhart, C., Lazenby, G., Schwebke, J., & Sobel, J. D. (2022) · Clinical Infectious Diseases · doi:10.1093/cid/ciab1057 · Cited by 149 · see citing works
Self-citationVaccines for human fungal diseases: close but still a long way to go
Oliveira, L. V. N., Wang, R., Specht, C. A., & Levitz, S. M. (2021) · npj Vaccines · doi:10.1038/s41541-021-00294-8 · Cited by 135 · see citing works
Treatment of Vulvovaginal Candidiasis—An Overview of Guidelines and the Latest Treatment Methods
Satora, M., Grunwald, A., Zaremba, B., Frankowska, K., Żak, K., Tarkowski, R., & Kułak, K. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12165376 · Cited by 84 · see citing works
Donders, G., Sziller, I. O., Paavonen, J., Hay, P., de Seta, F., Bohbot, J. M., Kotarski, J., Vives, J. A., Szabo, B., Cepuliené, R., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.934353 · Cited by 82 · see citing works
Clinical challenges in diagnosis and treatment of recurrent vulvovaginal candidiasis
Neal, C. M., & Martens, M. G. (2022) · SAGE Open Medicine · doi:10.1177/20503121221115201 · Cited by 56 · see citing works
Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response
Mercer, D. K., & O'Neil, D. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02177 · Cited by 50 · see citing works
Treatment for recurrent vulvovaginal candidiasis (thrush)
Cooke, G., Watson, C., Deckx, L., Pirotta, M., Smith, J., & van Driel, M. L. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009151.pub2 · Cited by 48 · see citing works
Zhao, G., Lyu, J., Veniaminova, N. A., Zarnowski, R., Mattos, E., Johnson, C. J., Quintanilla, D., Hautau, H., Hold, L. A., Xu, B., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60876-1 · Cited by 32 · see citing works
Self-citationImmunomodulation as a Therapy for Aspergillus Infection: Current Status and Future Perspectives
Lauruschkat, C. D., Einsele, H., & Loeffler, J. (2018) · Journal of Fungi · doi:10.3390/jof4040137 · Cited by 32 · see citing works
Regidor, P. A., Thamkhantho, M., Chayachinda, C., & Palacios, S. (2023) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443615.2023.2195001 · Cited by 31 · see citing works
- Authors
- Edwards, J. E., Schwartz, M. M., Schmidt, C. S., Sobel, J. D., Nyirjesy, P., Schodel, F., Marchus, E., Lizakowski, M., DeMontigny, E. A., Hoeg, J., Holmberg, T., Cooke, M. T., Hoover, K., Edwards, L., Jacobs, M., Sussman, S., Augenbraun, M., Drusano, M., Yeaman, M. R., Ibrahim, A. S., Filler, S. G., & Hennessey, J. P.
- Affiliations
- University of California, Los Angeles (US)
- NovaDigm Therapeutics (United States) (US)
- Wayne State University (US)
- Drexel University (US)
- Philimmune LLC, Philadelphia, Pennsylvania
- Miami Clinical Research, Corp, Florida
- Suffolk Obstetrics & Gynecology, Port Jefferson, New York
- TMC Life Research, Inc., Houston, Texas
- Lawrence OB-GYN Clinical Research, LLC, Lawrenceville, New Jersey
- Research Foundation of SUNY, Albany, New York
- Community Medical Research LLC, Miami Beach, Florida
- Corresponding author
- Hennessey, John P
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-04-25
- Volume
- 66
- Issue
- 12
- Pages
- 1928-1936
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC5982716
- OpenAlex
- W2799555303
- Cited by
- 213
- References
- 23
- Citations by year
- 2026: 26 · 2025: 36 · 2024: 24 · 2023: 37 · 2022: 23 · 2021: 27 · 2020: 15 · 2019: 15 · 2018: 10
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Health (2R42 AI071554-02A1, R01 AI19990, R01 AI063382)
- Department of Defense (W81XWH-11-1-0686)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- recurrent vulvovaginal candidiasis, Candida albicans, fungal vaccines, mucosal candidiasis, vaccine safety, women over 40
- MeSH terms
- Immunogenicity, Vaccine, Adolescent, Adult, B-Lymphocytes, Candida albicans, Candidiasis, Vulvovaginal, Double-Blind Method, Female, Fungal Proteins, Fungal Vaccines, Humans, Immunotherapy, Injections, Intramuscular, Middle Aged, Recurrence, T-Lymphocytes, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
