Huang W J, Zhang H Y, Harrison T J, Lan H Y, Huang G Y, Wang Y C
Department of Cell Biology, National Institute for the Control of Pharmaceutical and Biological Products, No. 2 Tiantanxili, Chongwen District, 100050, Beijing, China.
Arch Virol. 2009;154(3):481-8. doi: 10.1007/s00705-009-0335-7. Epub 2009 Feb 25.
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 microg) 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.
几种源自戊型肝炎病毒（HEV）1型毒株的抗原已在灵长类动物和人类中显示出对戊型肝炎的免疫原性和疗效。然而，源自HEV 4型的疫苗的保护作用尚未得到研究。本研究旨在评估源自HEV毒株T1（4型）的T1-ORF2（56 kDa）衣壳蛋白在恒河猴中的免疫原性和保护效力。相隔4周给予两剂（40微克）明矾吸附的T1-ORF2衣壳蛋白。首次给药后1-2周，所有免疫的猴子均发生血清转化。抗HEV IgG的峰值水平在第二次给药后2-3周出现，范围为5.7至196.0 U/ml。所有猴子对第二次给药均表现出回忆性抗体反应。用盐水免疫的对照猴子在整个攻击前期间HEV抗体均为阴性。给免疫的猴子静脉注射HEV 1型和4型。用T1-ORF2免疫的猴子在用5×10⁴个基因组当量的HEV攻击后，无论基因型如何，均受到保护免于感染和肝炎。在用5×10⁵个基因组当量的HEV 4型攻击后，与用盐水免疫的对照猴子相比，用T1-ORF2免疫的猴子丙氨酸转氨酶水平升高的时间较短，粪便排毒持续时间较短。总之，这些结果表明，在恒河猴中，HEV 4型的T1-ORF2衣壳蛋白与源自HEV 1型的其他候选疫苗具有相似的交叉保护作用。
