title: A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.
abstract: Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P ≤ 0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria.
authors.affiliation: Plant Physiology Laboratory, Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil; Faculty of Pharmacy, UFRGS, Av. Ipiranga 2752, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Anna Carolina A
authors.initials: AC
authors.lastname: Yendo
authors.affiliation: Plant Physiology Laboratory, Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil; Faculty of Pharmacy, UFRGS, Av. Ipiranga 2752, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: de Costa
authors.affiliation: Fepagro Animal Health - Institute of Veterinary Research "Desidério Finamor" (IPVDF), Estrada do Conde 6000, Eldorado do Sul, RS 92990-000, Brazil; Virology Laboratory, Microbiology Department, ICBS/UFRGS, Av. Sarmento Leite, 500, Porto Alegre, RS 90070-150, Brazil.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Cibulski
authors.affiliation: Fepagro Animal Health - Institute of Veterinary Research "Desidério Finamor" (IPVDF), Estrada do Conde 6000, Eldorado do Sul, RS 92990-000, Brazil; Virology Laboratory, Microbiology Department, ICBS/UFRGS, Av. Sarmento Leite, 500, Porto Alegre, RS 90070-150, Brazil.
authors.forename: Thais F
authors.initials: TF
authors.lastname: Teixeira
authors.affiliation: Plant Physiology Laboratory, Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Luana C
authors.initials: LC
authors.lastname: Colling
authors.affiliation: Laboratory of Carbohydrates and Glycoconjugates, Hygiene Institute, Universidad de la Republica (UdelaR), Montevideo, Av. Dr. Alfredo Navarro, 3051 Montevideo, Uruguay.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Mastrogiovanni
authors.affiliation: Laboratory of Carbohydrates and Glycoconjugates, Hygiene Institute, Universidad de la Republica (UdelaR), Montevideo, Av. Dr. Alfredo Navarro, 3051 Montevideo, Uruguay.
authors.forename: Silvia
authors.initials: S
authors.lastname: Soulé
authors.affiliation: Fepagro Animal Health - Institute of Veterinary Research "Desidério Finamor" (IPVDF), Estrada do Conde 6000, Eldorado do Sul, RS 92990-000, Brazil; Virology Laboratory, Microbiology Department, ICBS/UFRGS, Av. Sarmento Leite, 500, Porto Alegre, RS 90070-150, Brazil.
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Roehe
authors.affiliation: Faculty of Pharmacy, UFRGS, Av. Ipiranga 2752, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Grace
authors.initials: G
authors.lastname: Gosmann
authors.affiliation: Laboratory of Carbohydrates and Glycoconjugates, Hygiene Institute, Universidad de la Republica (UdelaR), Montevideo, Av. Dr. Alfredo Navarro, 3051 Montevideo, Uruguay.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Ferreira
authors.affiliation: Plant Physiology Laboratory, Center for Biotechnology and Department of Botany, Federal University of Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Porto Alegre, RS 91501-970, Brazil. Electronic address: fettneto@cbiot.ufrgs.br.
authors.forename: Arthur G
authors.initials: AG
authors.lastname: Fett-Neto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001921:Brain / Q000821:virology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D031990:Quillaja / Q000737:chemistry; D062605:Quillaja Saponins / Q000008:administration & dosage / Q000737:chemistry*; D012367:RNA, Viral / Q000302:isolation & purification; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D010936:Plant Extracts; D062605:Quillaja Saponins; D012367:RNA, Viral; D011819:Rabies Vaccines; C046386:Quil A
keywords: Adjuvant; Challenge; Protection; Quillaja brasiliensis; Rabies virus; Saponin