Rharbaoui Faiza, Drabner Birgit, Borsutzky Stefan, Winckler Urte, Morr Michael, Ensoli Barbara, Mühlradt Peter F, Guzmán Carlos A
Vaccine Research Group, Division of Microbiology, GBF-German Research Center for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Eur J Immunol. 2002 Oct;32(10):2857-65. doi: 10.1002/1521-4141(2002010)32:10<2857::AID-IMMU2857>3.0.CO;2-R.
The adjuvanticity of MALP-2, a 2-kDa synthetic lipopeptide with macrophage-stimulatory activity, was evaluated in BALB/c mice using beta-galactosidase (beta-gal) as model antigen. When co-administered with beta-gal by either the intranasal (i.n.) or i.p. route, MALP-2 (0.5 microg) was capable of increasing beta-gal-specific serum IgG titers by 675-3,560-fold (i.n.) and 64-128-fold (i.p.), respectively, as compared to immunization with beta-gal alone. Using MALP-2, almost maximal IgG responses were already stimulated following the first immunization, and the IgG titers were similar to those observed using 10 microg of cholera toxin B subunit (CTB) as adjuvant. The mucosal immune system was also effectively stimulated (p<0.05) when MALP-2 was administered by the i.n. route (36% and 23% of beta-gal-specific IgA in lung and vaginal lavages, respectively). The i.n. co-administration of MALP-2 stimulated a stronger cellular immune response than CTB, both in submandibular lymph nodes and spleen (p<0.05). The analysis of beta-gal-specific IgG isotypes and the profiles of cytokines secreted by in vitro re-stimulated cells showed that co-administration of MALP-2 triggered a dominant Th2-response pattern. A recruitment of B220(+) and MAC-1(+) cells with an up-regulated expression of MHC class I, CD80 (B7.1) and CD54 (ICAM-1) was observed in nasal associated lymphoid tissues from MALP-2 treated mice. Taken together, our results demonstrated that the synthetic lipopeptide MALP-2 represents a very promising adjuvant for the mucosal delivery of vaccine antigens.
使用β-半乳糖苷酶（β-gal）作为模型抗原，在BALB/c小鼠中评估了具有巨噬细胞刺激活性的2 kDa合成脂肽MALP-2的佐剂活性。与单独用β-gal免疫相比，当通过鼻内（i.n.）或腹腔内（i.p.）途径与β-gal共同给药时，MALP-2（0.5微克）能够使β-gal特异性血清IgG滴度分别提高675 - 3560倍（i.n.）和64 - 128倍（i.p.）。使用MALP-2时，首次免疫后几乎就刺激产生了最大的IgG反应，且IgG滴度与使用10微克霍乱毒素B亚单位（CTB）作为佐剂时观察到的滴度相似。当通过i.n.途径给药MALP-2时，黏膜免疫系统也受到了有效刺激（p<0.05）（肺和阴道灌洗液中β-gal特异性IgA分别占36%和23%）。在颌下淋巴结和脾脏中，i.n.共同给药MALP-2比CTB刺激产生更强的细胞免疫反应（p<0.05）。对β-gal特异性IgG同种型的分析以及体外再刺激细胞分泌的细胞因子谱显示，共同给药MALP-2引发了占主导地位的Th2反应模式。在接受MALP-2治疗的小鼠的鼻相关淋巴组织中，观察到B220(+)和MAC-1(+)细胞募集，同时MHC I类、CD80（B7.1）和CD54（ICAM-1）的表达上调。综上所述，我们的结果表明，合成脂肽MALP-2是一种非常有前景的用于疫苗抗原黏膜递送的佐剂。
