NDV-3 protects mice from vulvovaginal candidiasis through T- and B-cell immune response.
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.
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.
Ashraf S
AS
Ibrahim
Guanpingsheng
G
Luo
Teclegiorgis
T
Gebremariam
Hongkyu
H
Lee
Clint S
CS
Schmidt
John P
JP
Hennessey
Samuel W
SW
French
Michael R
MR
Yeaman
Scott G
SG
Filler
John E
JE
Edwards
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D002181:Candidiasis, Vulvovaginal / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000276:immunology*; D005657:Fungal Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D044967:Serum / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology
C113620:ALS3 protein, Candida albicans; D005656:Fungal Proteins; D005657:Fungal Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic
Als3; Candida albicans; Murine; NDV-3; VVC