不同佐剂流感疫苗的小鼠免疫效果

Immune effect of influenza vaccine with various adjuvant in mice

目的评价不同佐剂流感疫苗的小鼠免疫效果。方法培养并纯化流感病毒鼠肺适应株PR/8/34,制备流感病毒裂解液。将BALB/c小鼠随机分为5组:流感病毒PR/8/34裂解液(HA)组、HA+大肠杆菌不耐热肠毒素b亚单位(Heat-labile exterotoxin B subunit,LTB)组、HA+弗氏不完全佐剂(FIA)组、HA+A(lOH)3组和生理盐水对照组,HA+LTB组采用滴鼻黏膜免疫,免疫剂量为50μl/只,其余各组均采用肌肉注射,免疫剂量为100μl/只,共免疫2次,间隔2周。于初次免疫后28 d,经小鼠眼内眦采血,分离血清,检测各组小鼠血清IgG抗体效价、血凝抑制效价及攻毒后保护力及鼠肺病毒RNA载量,评价不同佐剂对流感疫苗的免疫增强作用。结果各佐剂组小鼠血清IgG抗体水平及血凝抑制效价均显著高于HA组,且差异均有统计学意义(P均<0.01);HA+FIA组小鼠血清IgG抗体水平及血凝抑制效价均显著高于HA+LTB组和HA+A(lOH)3组(P均<0.01);HA+LTB组与HA+A(l OH)3组抗体效价差异无统计学意义(P>0.05)。各佐剂组和HA组小鼠攻毒后均存活,HA+FIA组鼠肺病毒RNA载量最低,HA+LTB组与HA+A(lOH)3组相当。结论不同佐剂对流感疫苗均有一定的免疫增强作用,其中LTB滴鼻免疫和A(lOH)3肌肉注射对流感疫苗的免疫增强作用相当。

Objective To evaluate the immune effect of influenza vaccine with various adjuvant in mice.Methods BALB / c mice were randomly divided into split influenza virus PR8 / 34（HA）,HA ＋ LTB,HA ＋ FIA,HA ＋ Al（OH）3 and physiological saline groups.The mice in HA group were immunized by intranasal drip,at a dosage of 50 μl,while those in other groups by intramuscular injection,each at a dosage of 100 μl,for 2 times at an interval of 2 weeks.Serum samples were collected 28 d after the first immunization and determined for IgG and HI titers.Meanwhile,the protection against virus challenge and the viral RNA load in lung were analyzed,based on which the immunopotentiations of various adjuvant to influenza vaccine were evaluated.Results The IgG and HI titers were significantly higher in HA ＋ LTB,HA ＋ FIA,HA ＋ Al（OH）3 groups than in HA group（P 0.01）,and in HA ＋ FIA group than in HA ＋ LTB and HA ＋ Al（OH）3 groups（P 0.01）.However,the IgG titer in HA ＋ LTB group was equivalent to that in HA ＋ Al（OH）3 group（P 0.05）.All the mice in HA,HA ＋ LTB,HA ＋ FIA,HA ＋ Al（OH）3 groups survived the virus challenge.The viral RNA load was the lowest in HA ＋ FIA group,while were similar in HA ＋ LTB and HA ＋ Al（OH）3 groups.Conclusion Various adjuvant showed certain immunopotentiations to influenza vaccine.However,the immunopotentiation of LTB by intranasal drip was equivalent to that of Al（OH）3 by intramuscular injection.