Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4
Immunogenicity and protective efficacy in rhesus monkeys of a recombinant ORF2 protein from hepatitis E virus genotype 4
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DOI：
10.1007/s00705-009-0335-7
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发表时间：
2009-03-01
影响因子：
2.7
通讯作者：
Wang, Y. C.
中科院分区：
文献类型：
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作者：
Huang, W. J.;Zhang, H. Y.;Wang, Y. C.
从戊型肝炎病毒（HEV）基因型1株中提取的几种抗原在灵长类动物和人类中显示出对戊型肝炎的免疫原性和有效性。然而，从HEV基因型4衍生的疫苗的保护作用尚未得到研究。本研究旨在评价HEV T1（基因型4）衣壳蛋白T1- orf2 （56 kDa）在恒河猴体内的免疫原性和保护作用。铝吸附T1-ORF2衣壳蛋白40 μ g，每隔4周给药2次。所有免疫的猴子在第一次注射后1-2周发生血清转化。抗hev IgG在第二次给药后2-3周出现峰值，范围为5.7 ~ 196.0 U/ml。所有猴子对第二次注射都表现出遗忘性抗体反应。用生理盐水免疫的对照猴在整个攻击前期间HEV抗体均为阴性。免疫后的猴子静脉注射HEV基因1型和4型病毒。无论基因型如何，接种T1-ORF2的猴子在受到5 × 10(4)个基因组当量的HEV攻击后，都不会感染和肝炎。在用5 × 10(5)个基因组当量的HEV基因型4攻击后，与用生理盐水免疫的对照猴子相比，接种T1-ORF2的猴子丙氨酸转氨酶水平升高的时间更短，粪便排出的时间也更短。总之，这些结果表明，在恒河猴中，HEV基因型4的T1-ORF2衣壳蛋白与HEV基因型1衍生的其他候选疫苗具有相似的交叉保护作用。
Several antigens derived from hepatitis E virus (HEV) genotype 1 strains have shown immunogenicity and efficacy against hepatitis E in primates and humans. However, the protective effect of a vaccine derived from HEV genotype 4 has not been studied. This study aimed to evaluate the immunogenicity and protective efficacy of the T1-ORF2 (56 kDa) capsid protein derived from HEV strain T1 (genotype 4) in rhesus monkeys. Two doses (40 mu g) of alum-absorbed T1-ORF2 capsid protein were administered 4 weeks apart. Seroconversion occurred in all immunized monkeys 1-2 weeks after the first dose. The peak levels of anti-HEV IgG appeared at 2-3 weeks after the second dose and ranged from 5.7 to 196.0 U/ml. All monkeys showed an anamnestic antibody response to the second dose. Control monkeys immunized with saline remained negative for HEV antibodies throughout the pre-challenge period. The immunized monkeys were challenged intravenously with HEV genotypes 1 and 4. Monkeys immunized with T1-ORF2 were protected from infection and hepatitis after challenge with 5 x 10(4) genome equivalents of HEV, regardless of the genotype. After challenge with 5 x 10(5) genome equivalents of HEV genotype 4, the monkeys immunized with T1-ORF2 had a shorter period of raised alanine aminotransferase levels and a shorter duration of fecal shedding compared to control monkeys immunized with saline. In conclusion, these results suggest that, in rhesus monkeys, the T1-ORF2 capsid protein of HEV genotype 4 has similar cross-protective effects to other candidate vaccines derived from HEV genotype 1.