Xu Zhi-Yi, Wang Xuan-Yi
Institutes of Biomedical Sciences; Shanghai Medical College; Fudan University; Shanghai, PR China; Department of Epidemiology; School of Public Health, Fudan University; Shanghai, PR China.
Hum Vaccin Immunother. 2014;10(3):659-66. doi: 10.4161/hv.27124. Epub 2013 Nov 26.
Two live, attenuated hepatitis A vaccines, H 2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H 2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of the H 2 strain or for marmoset-to-marmoset transmission of LA-1 strain, by close contact. H 2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in China for 14 years following introduction of the H 2 live vaccine into the Expanded Immunization Program (EPI) in 1992.
两种甲型肝炎减毒活疫苗，H2和LA - 1病毒株，分别通过在32℃和35℃的细胞培养物中对病毒进行连续传代而研制。两种疫苗均安全且具有免疫原性，皮下注射单剂量即可为95%的接种者提供针对临床甲型肝炎的保护。疫苗接种者无法免受无症状、亚临床甲型肝炎病毒（HAV）感染，这种感染诱导的抗体反应与未接种疫苗的受试者相似。第二剂可引起回忆反应，可用于加强免疫。用H2疫苗对人进行口服免疫或用LA - 1疫苗对狨猴进行口服免疫均失败，且未发现通过密切接触H2毒株在人与人之间传播或LA - 1毒株在狨猴与狨猴之间传播的证据。H2毒株在狨猴、人或37℃的细胞培养物中传代时基因稳定；该病毒在狨猴中连续传代3次未引起毒力突变。活疫苗具有成本低、单剂量注射、长期保护以及通过亚临床感染延长免疫持续时间等优点。改善卫生条件并向儿童接种1.5亿剂活疫苗，使得中国在1991年至2006年的16年期间，甲型肝炎的全国年发病率降低了90%。2008年，甲型肝炎活疫苗和灭活疫苗免疫均纳入国家儿童常规免疫规划，每年约1600万例出生儿童中有92%在18月龄时接种了价格低廉的减毒活疫苗。自1992年将H2活疫苗引入扩大免疫规划（EPI）后，中国在14年的时间里实现了该疾病的近乎消除。
