Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines.
Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 microg) was intranasally (i.n.) inoculated with influenza vaccine (10 microg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3-14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 microg) was i.n. inoculated with the vaccine (10 microg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27-50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 microg) and influenza HA vaccine (1 microg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 microg) each and diphtheria-pertussis-tetanus (DPT) vaccine (10 microg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 microg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.
Nagai
T
T
Oriental Medicine Research Center, The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, 108-8642, Tokyo, Japan.
Suzuki
Y
Y
Kiyohara
H
H
Susa
E
E
Kato
T
T
Nagamine
T
T
Hagiwara
Y
Y
Tamura
S
S
Yabe
T
T
Aizawa
C
C
Yamada
H
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000302:isolation & purification*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology; D002642:Chick Embryo; D002851:Chromatography, High Pressure Liquid; D003353:Corynebacterium diphtheriae / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000737:chemistry / Q000276:immunology*; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006462:Hemolytic Plaque Technique; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D015394:Molecular Structure; D009297:Nasal Mucosa / Q000276:immunology; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry*; D029608:Polygalaceae / Q000737:chemistry*; D012503:Saponins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D012756:Sheep; D012997:Solvents; D013045:Species Specificity; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D014867:Water
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D010936:Plant Extracts; D012503:Saponins; D012997:Solvents; D014315:Triterpenes; C442859:onjisaponin F; D014867:Water