Miller Darren S, Kotlarski Ieva, Jilbert Allison R
Hepatitis Virus Research Laboratory, School of Molecular and Biomedical Science, University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
Virology. 2006 Jul 20;351(1):159-69. doi: 10.1016/j.virol.2006.02.037. Epub 2006 Apr 19.
We tested the efficacy of DNA vaccines expressing the duck hepatitis B virus (DHBV) pre-surface (pre-S/S) and surface (S) proteins in modifying the outcome of infection in 14-day-old ducks. In two experiments, Pekin Aylesbury ducks were vaccinated on days 4 and 14 of age with plasmid DNA vaccines expressing either the DHBV pre-S/S or S proteins, or the control plasmid vector, pcDNA1.1Amp. All ducks were then challenged intravenously on day 14 of age with 5 x 10(7) or 5 x 10(8) DHBV genomes. Levels of initial DHBV infection were assessed using liver biopsy tissue collected at day 4 post-challenge (p.c.) followed and immunostained for DHBV surface antigen to determine the percentage of infected hepatocytes. All vector vaccinated ducks challenged with 5 x 10(7) and 5 x 10(8) DHBV genomes had an average of 3.21% and 20.1% of DHBV-positive hepatocytes respectively at day 4 p.c. and 16 out of 16 ducks developed chronic DHBV infection. In contrast, pre-S/S and S vaccinated ducks challenged with 5 x 10(7) DHBV genomes had reduced levels of initial infection with an average of 1.38% and 1.93% of DHBV-positive hepatocytes at day 4 p.c. respectively and 10 of 18 ducks were protected against chronic infection. The pre-S/S and the S DNA vaccinated ducks challenged with 5 x 10(8) DHBV genomes had an average of 31.5% and 9.2% of DHBV-positive hepatocytes on day 4 p.c. respectively and only 4 of the 18 vaccinated ducks were protected against chronic infection. There was no statistically significant difference in the efficacy of the DHBV pre-S/S or S DNA vaccines. In conclusion, vaccination of young ducks with DNA vaccines expressing the DHBV pre-S/S and S proteins induced rapid immune responses that reduced the extent of initial DHBV infection in the liver and prevented the development of chronic infection in a virus dose-dependent manner.
我们测试了表达鸭乙型肝炎病毒(DHBV)前S(pre - S/S)和S蛋白的DNA疫苗在改变14日龄鸭感染结果方面的效力。在两项实验中,北京艾尔斯伯里鸭在4日龄和14日龄时用表达DHBV前S/S或S蛋白的质粒DNA疫苗或对照质粒载体pcDNA1.1Amp进行免疫接种。然后所有鸭在14日龄时静脉注射5×10⁷或5×10⁸个DHBV基因组进行攻毒。使用攻毒后第4天(p.c.)采集的肝活检组织评估初始DHBV感染水平,随后对其进行免疫染色以检测DHBV表面抗原,从而确定被感染肝细胞的百分比。所有接种载体疫苗并分别用5×10⁷和5×10⁸个DHBV基因组攻毒的鸭在攻毒后第4天,平均分别有3.21%和20.1%的DHBV阳性肝细胞,并且16只鸭中有16只发展为慢性DHBV感染。相比之下,用5×10⁷个DHBV基因组攻毒的接种前S/S和S疫苗的鸭初始感染水平降低,攻毒后第4天平均分别有1.38%和1.93%的DHBV阳性肝细胞,并且18只鸭中有10只受到保护未发生慢性感染。用5×10⁸个DHBV基因组攻毒的接种前S/S和S DNA疫苗的鸭在攻毒后第4天平均分别有31.5%和9.2%的DHBV阳性肝细胞,并且18只接种疫苗的鸭中只有4只受到保护未发生慢性感染。DHBV前S/S或S DNA疫苗的效力没有统计学上的显著差异。总之,用表达DHBV前S/S和S蛋白的DNA疫苗对幼鸭进行免疫接种可诱导快速免疫反应,以病毒剂量依赖的方式降低肝脏中初始DHBV感染的程度并预防慢性感染的发生。