隆安县乙肝疫苗免疫逃避株的研究

Vaccine-induced escape mutant of hepatitis B virus in Long An County

目的查明隆安县部分乙肝疫苗免疫失败的原因。方法用套式PCR(nPCR)扩增41例隆安县接受乙肝疫苗免疫的儿童及其母亲血清HBVS基因 ,阳性者用直接测序法测序。结果23例HBVDNA阳性 ,阳性率为56%(23/41) ;表面抗原的4个主要亚型 (adr、adw、ayr、ayw)都出现在本研究中 ,其中以adw为主 ,占65.2 %(15/23) ,标本3及27儿童感染的亚型 (adw)不同于他们母亲感染的亚型 (adr及ayw) ;标本46兄弟俩及标本37均在aa145发生突变 (甘氨酸→精氨酸 ) ,标本64也在aa145发生突变 (甘氨酸→丙氨酸 )。另外 ,标本38在aa120发生突变 (脯氨酸→丝氨酸 ) ,标本27在aa129发生突变 (谷氨酰胺→精氨酸 )。结论隆安县存在乙肝疫苗免疫逃避株 ,提示免疫逃避株的产生是隆安县部分乙肝疫苗免疫失败的原因之一 ,这些免疫逃避株是目前阻断乙肝病毒母婴传播的难点。

Objective To find out the cause of breakthrough infections in Long An County children immunized with hepatitis B vaccine. Methods The nested polymerase chain reaction(nPCR) was used to amplify HBV DNA S gene in sera from 41 cases(children immunized with hepatitis B vaccine and their mothers) from Long An County, and then HBV DNA nPCR products were sequenced by direct sequencing. Results HBV DNA positive rate of the cases was 56%.Four major serotypes of HBsAg (adr、adw、ayr、ayw) were all present in our study but adw accounted for 65.2%(15/23).Serotypes of sample 3 and 27(adw) were different from those of their mothers (adr & ayw).The mutation at aa 145 (Glycine→Arginine) presented in sample 37,46 and his brother while Glycine→Alanine at the same position presented in sample 64. The other mutations presented in sample 38(Proline→Serine),27(Glutamine→Arginine). Conclusion There exist vaccine-induced escape mutants of hepatitis B virus in Long An County. It is suggested that these mutants are part of the cause of breakthrough infections in Long An County children immunized with hepatitis B vaccine. It is currently difficulty to stop vertical transmission of these mutants.