McArthur J, Schulze K, Chin J, Currie B J, Sriprakash K S, Talay S R, Chhatwal G S, Guzmán C A, Walker M J
Department of Biological Sciences, University of Wollongong, Braunschweig, Germany.
Indian J Med Res. 2004 May;119 Suppl:115-20.
BACKGROUND & OBJECTIVES: The fibronectin binding protein Sfb1 of Streptococcus pyogenes is a well characterised antigen which induces protection against lethal challenge with group A streptococcus (GAS) when adjuvanted with cholera toxin B-subunit (CTB). As an alternative to CTB adjuvanted intranasal immunisations we investigated the immune responses generated in mice using Sfb1 incorporated in to the skin and mucosal adjuvant SAMA4.
Mice (BALB/c) were vaccinated intradermally with 100 microl of either SAMA4 (adjuvant only group) or SAMA4/Sfb1 and were boosted 7 days later. Mice vaccinated with CTB based vaccines were immunised by intranasal inoculation with a mixture containing 30 microg Sfb1 and 10 microg CTB on days 1, 3, 5 and 15. At 14 days after the last booster immunisation the immune response was characterised and mice were challenged with 10(8) CFU of S. pyogenes.
Mice vaccinated with SAMA4/Sfb1 elicited a Sfb1-specific IgG response in the sera that was significantly higher than that seen in control mice and mice immunised with the adjuvant only (P<0.05). No significant differences were seen for specific IgA antibodies in the sera in all groups examined. Compared with non-immunised and adjuvant only immunised controls, mice immunised with the Sfb1/SAMA4 vaccine exhibited a significant increase (P<0.05) in the number of Sfb1 reactive spleen cells in lymphoproliferation assays which were three fold higher than those seen for mice vaccinated with the Sfb1/CTB vaccine. Mice vaccinated with CTB/Sfb1 had the highest level of protection (80%) as where mice vaccinated with SAMA4 and SAMA4/Sfb1 displayed no protection (20% and 40%).
INTERPRETATION & CONCLUSION: These data suggest that the SAMA4 adjuvant used in this study fails to elicit protective immunity in BALB/c mice when used to adjuvant the known protective antigen Sfb1.
化脓性链球菌的纤连蛋白结合蛋白Sfb1是一种特征明确的抗原，当与霍乱毒素B亚单位（CTB）联合作为佐剂时，可诱导对A组链球菌（GAS）致死性攻击的保护作用。作为CTB佐剂鼻内免疫的替代方法，我们研究了将Sfb1掺入皮肤和粘膜佐剂SAMA4后在小鼠体内产生的免疫反应。
将100微升SAMA4（仅佐剂组）或SAMA4/Sfb1皮内接种给小鼠（BALB/c），并在7天后加强免疫。用基于CTB的疫苗接种的小鼠在第1、3、5和15天通过鼻内接种含有30微克Sfb1和10微克CTB的混合物进行免疫。在最后一次加强免疫后14天，对免疫反应进行表征，并对小鼠用10⁸CFU的化脓性链球菌进行攻击。
用SAMA4/Sfb1接种的小鼠血清中引发了Sfb1特异性IgG反应，该反应明显高于对照小鼠和仅用佐剂免疫的小鼠（P<0.05）。在所有检测组的血清中，特异性IgA抗体未见明显差异。与未免疫和仅用佐剂免疫的对照相比，用Sfb1/SAMA4疫苗免疫的小鼠在淋巴细胞增殖试验中Sfb1反应性脾细胞数量显著增加（P<0.05），比用Sfb1/CTB疫苗接种的小鼠高两倍。用CTB/Sfb1接种的小鼠具有最高水平的保护作用（80%），而用SAMA4和SAMA4/Sfb1接种的小鼠没有保护作用（20%和40%）。
这些数据表明，本研究中使用的SAMA4佐剂在用于佐剂已知的保护性抗原Sfb1时，未能在BALB/c小鼠中引发保护性免疫。
