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Vaccine. 2013 Nov 12;31(47):5549-56. doi: 10.1016/j.vaccine.2013.09.016. Epub 2013 Sep 21.

NDV-3 protects mice from vulvovaginal candidiasis through T- and B-cell immune response.

Author information

1
The Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center and the St. John's Cardiovascular Research Center, Torrance, CA, United States; David Geffen School of Medicine at UCLA, Los Angeles, CA, United States. Electronic address: ibrahim@labiomed.org.

Abstract

We have previously reported that vaccination with rAls3p-N protein of Candida albicans, formulated with alum adjuvant (also designated as NDV-3) protects immunocompetent mice from, lethal disseminated candidiasis and mucosal oropharyngeal candidiasis. NDV-3 vaccine was recently, tested in a Phase 1 clinical trial and found to be safe, well-tolerated, and induced robust humoral and, cellular immune responses with increased interferon (IFN)-gamma and interleukin (IL)-17 secretion. In preparation for a Phase 2 clinical trial against vulvovaginal candidiasis (VVC), we evaluated NDV-3, efficacy in a murine VVC model. Here, NDV-3 induced a strong immune response characterized by high, anti-rAls3p-N serum IgG and vaginal IgA titers. Furthermore, moderate doses of the vaccine (a range of 1-30μg given subcutaneously [SQ] or 0.3-10μg given intramuscularly [IM]) elicited a 10-1000 fold, decrease in vaginal fungal burden vs. control (mice injected with alum adjuvant alone) in both inbred, and outbred mice infected with different clinical C. albicans isolates. Additionally, NDV-3 required both, T and B lymphocytes for efficacy in reducing C. albicans tissue burden, which is followed by a reduction, in neutrophil influx to the affected site. Finally, anti-rAls3p-N antibodies enhanced the ex vivo killing, of C. albicans by neutrophils primed with IFN-gamma. These data indicate that NDV-3 protects mice, from VVC by a mechanism that involves the concerted priming of both humoral and adaptive immune, responses.

KEYWORDS:

Als3; Candida albicans; Murine; NDV-3; VVC

PMID:
24063977
PMCID:
PMC3866209
DOI:
10.1016/j.vaccine.2013.09.016
[Indexed for MEDLINE]
Free PMC Article

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