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

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.

• Authors: Ashraf S Ibrahim, Guanpingsheng Luo, Teclegiorgis Gebremariam, Hongkyu Lee, Clint S Schmidt, John P Hennessey Jr, Samuel W French, Michael R Yeaman, Scott G Filler, John E Edwards Jr
• Journal: Vaccine (Vaccine) Vol. 31 Issue 47 Pg. 5549-56 (Nov 12 2013) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 24063977 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• ALS3 protein, Candida albicans
• Fungal Proteins
• Fungal Vaccines
• Immunoglobulin A
• Immunoglobulin G
• Vaccines, Synthetic

Topics

• Animals
• B-Lymphocytes (immunology)
• Candida albicans (genetics, immunology)
• Candidiasis, Vulvovaginal (immunology, prevention & control)
• Female
• Fungal Proteins (genetics, immunology)
• Fungal Vaccines (administration & dosage, genetics, immunology)
• Immunoglobulin A (analysis)
• Immunoglobulin G (blood)
• Injections, Intramuscular
• Injections, Subcutaneous
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Serum (immunology)
• T-Lymphocytes (immunology)
• Vaccines, Synthetic (administration & dosage, genetics, immunology)
• Vagina (immunology)