Ugozzoli M, O'Hagan D T, Ott G S
Chiron Corporation, Emeryville, CA 94608, USA.
Immunology. 1998 Apr;93(4):563-71. doi: 10.1046/j.1365-2567.1998.00441.x.
Mucosal immunization offers the potential for inducing IgA antibody responses in the vagina, the site of infection for many viruses, including herpes simplex type 2 (HSV-2). To investigate this possibility, mice were immunized intranasally with 10 micrograms glycoprotein D2 (gD2) from HSV combined with a series of adjuvants of proven efficacy; the oil in water emulsion MF59, poly(D,L-lactide-co-glycolide) microparticles (PLG) (encapsulated or co-administered), immune-stimulating complexes (iscoms) (incorporated or co-administered with iscomatrix) and the genetically detoxified enterotoxin from Escherichia coli, LT-K63. Encapsulation of gD2 into PLG microparticles, incorporation of gD2 into iscoms and co-administration of gD2 with LT-K63 induced mucosal IgA antibody responses (nasal wash, saliva and vaginal wash) which were greater than those induced by intramuscular administration of gD2 with MF59. Intranasal immunization with these formulations also induced substantial levels of serum IgG and neutralizing antibodies. These studies demonstrated that intranasal immunization with potent adjuvants is an effective means to induce mucosal antibody responses, even in the lower genital tract.
黏膜免疫具有在阴道诱导产生IgA抗体反应的潜力,阴道是包括单纯疱疹病毒2型(HSV-2)在内的多种病毒的感染部位。为了探究这种可能性,用10微克来自HSV的糖蛋白D2(gD2)与一系列已证实有效的佐剂经鼻免疫小鼠;水包油乳剂MF59、聚(D,L-丙交酯-共-乙交酯)微粒(PLG)(包封或共同给药)、免疫刺激复合物(iscoms)(掺入或与iscomatrix共同给药)以及来自大肠杆菌的基因解毒肠毒素LT-K63。将gD2包封到PLG微粒中、将gD2掺入iscoms以及将gD2与LT-K63共同给药诱导的黏膜IgA抗体反应(鼻腔冲洗液、唾液和阴道冲洗液)大于用gD2与MF59肌肉注射诱导的反应。用这些制剂经鼻免疫还诱导了高水平的血清IgG和中和抗体。这些研究表明,用强效佐剂经鼻免疫是诱导黏膜抗体反应的有效手段,即使在女性下生殖道也是如此。