Preferential distribution of these minor collagens in growth cartilage suggests a role in development during normal cartilage growth.Sulfolipo-cyclodextrin in squalane-in-water as a novel and safe vaccine Previously, we described synergistic adjuvanticity of combinations of synthetic sulfolipo(SL)-derivatives of polysaccharide (SL-polysaccharides) and squalane-in-water emulsions (squalane/W). In this paper, effects of type of polysaccharide and nature of oil on adjuvanticity, reactogenicity and stability are described. ordinary cleanser -derivatives of the following polysaccharides were synthesised: synthetic polysucroses with weight-average molecular weight (MW) of 400,000 (Ficoll400), 70,000 (Ficoll70) and 39,000 Da (Ficoll39), polyfructose of 5,000 Da (inulin), linear polyglucose of 1,200 Da (maltodextrin) and cyclic polyglucose of 1,135 Da (beta-cyclodextrin). The number of sulphate groups per monosaccharide of the different SL-polysaccharides varied between 05 and 03 and the number of lipid groups per monosaccharide between 15 and 19. the ordinary squalane cleanser were prepared by incorporating these SL-polysaccharides into oil-in-water emulsions of either squalane, hexadecane, soya oil or mineral oil.
Adjuvanticity of the formulations obtained for humoral responses to inactivated pseudorabies virus (PRV) and inactivated influenza virus strains A/Swine (A/Swine) and MRC-11 (MRC-11) in pigs and MRC-11 and ovalbumin (OVA) in mice depended on the type of oil (squalane = mineral oil > hexadecane = soya oil) but not on the type of polysaccharide backbone of the SL-derivative. Reactogenicity assessed by local swelling in mice decreased with decreasing MW (SL-Ficoll400 = Ficoll70 = Ficoll39 > SL-inulin = SL-maltodextrin > SL-cyclodextrin) when combined with squalane and decreased with the type of oil in the following order: squalane > mineral oil > hexadecane > soya oil when combined with SL-Ficoll400. Stability of the SL-polysaccharide/squalane/W emulsions at elevated temperature increased with decreasing MW of the SL-polysaccharide (SL-Ficoll400 < SL-Ficoll70 = SL-Ficoll39 < SL-inulin = SL-maltodextrin = SL-cyclodextrin). SL-cyclodextrin/squalane/W remained stable for > 2 years at 4 degrees C, > 18 weeks at 37 degrees C and > 10 days at 60 degrees C. We concluded that reactogenicity and stability but not adjuvanticity of SL-polysaccharide/squalane/W formulations depended on the MW of SL-polysaccharide and that SL-cyclodextrin/squalane/W is a promising non-mineral oil adjuvant as it combines strong adjuvanticity (i.e. better than the mineral oil-based adjuvant presently applied) with low reactogenicity and good Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza.
We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months-17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 35 μg of A/H1N1 antigen formulated with 50% MF59 (35_halfMF59) or 7 μg of A/H1N1 antigen formulated with 100% MF59 (7_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1-<3, 3-8, and 9-17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1-<3 and 3-8 y cohorts. Among children aged 6-11 months, 1 dose of 7_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 35_halfMF59 were required to achieve this result.
All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 35_halfMF59 (2 doses for children <12 months) and 7_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 35_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people.Assessment of the immunogenicity and safety of varying doses of an Japanese paediatric, adult and elderly subjects.Yotsuyanagi H, Kusadokoro H, Sawata H, Nakura N, Lattanzi M.INTRODUCTION: Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety vaccine in healthy Japanese paediatric, adult and elderly subjects.METHODS: One hundred and twenty-three children (6 months-18 years), and 200 adults (19-60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7 μg antigen with a full (95 mg) adjuvant dose, or 35 μg antigen with a half (475 mg) adjuvant dose.