RESUMO
Immunization of pregnant women with Group B Streptococcus (GBS) capsular polysaccharide (CPS) conjugate vaccine (CV) could protect young infants against invasive GBS disease. We evaluated the immunogenicity of investigational five GBS monovalent (serotypes Ia, Ib, II, III, and V) CPS-tetanus toxoid (TT)-CV with adjuvant and GBS pentavalent CPS-TT-CV with adjuvant (GBS5-CV-adj) and without adjuvant (GBS5-CV-no-adj), in Balb/c mice. Aluminum phosphate was the adjuvant in the formulations, where included. The homotypic immunoglobulin G (IgG) geometric mean concentration (GMC) and opsonophagocytic activity (OPA) geometric mean titer (GMT) did not differ after the third dose of the GBS5-CV-adj vaccine compared with the monovalent counterparts for all five serotypes. The GBS5-CV-adj induced higher post-vaccination serotype-specific IgG GMCs and OPA GMTs compared to GBS5-CV-no_adj. The GBS5-CV with and without adjuvant should be considered for further development as a potential vaccine for pregnant women to protect their infants against invasive GBS disease.
RESUMO
Liposomes form a major class of non-viral vectors for short interfering RNA delivery, however tissue and cell-specific targeting are additional requirements in the design of short interfering RNA delivery systems with a therapeutic potential. Selective delivery of liposomes to hepatocytes may be achieved by directing complexes to the asialoglycoprotein receptor, which is expressed on hepatocytes, and which displays high affinity for the ß-d-galactopyranosyl moiety. We aimed to show that the d-galactopyranosyl ring in direct ß-glycosidic link to cholesterol, when formulated into liposomes with 3ß[N-(N',N'-dimethylaminopropane) carbamoyl] cholesterol (Chol-T) or its quaternary trimethylammonium analogue (Chol-Q), may promote targeted delivery of cytotoxic short interfering RNA to the human hepatoma cell line HepG2 via the asialoglycoprotein receptor. Liposome-short interfering RNA interactions were characterized by electron microscopy, dye displacement, gel retardation and nuclease assays. Stable short interfering RNA-protective lipoplexes were formed at N/P ratios in the range 5:1-7:1. Targeted lipoplex 4 achieved high transfection efficiencies at 50 nm short interfering RNA (70%) and <10% in a competition assay, whilst untargeted complexes reached low levels at the same concentration (<25%). Transfection efficiencies of all lipoplexes in the asialoglycoprotein receptor-negative cell line HEK293 under the same conditions were low. Lipoplexes containing cholesteryl-ß-d-galactopyranoside may therefore form the basis for the development of useful hepatotropic short interfering RNA delivery vectors.