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韩国疫苗株与流行野毒株之间的交叉中和作用。

Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea.

机构信息

Division of Vaccine Research, Korea National Research Institute of Health, Korea Centers for Disease Control and Prevention, CheongJu, Chungcheongbuk-do, Republic of Korea.

Division of Viral Disease, Center for Laboratory Control of Infectious Disease, Korea Centers for Disease Control and Prevention, CheongJu, Chungcheongbuk-do, Republic of Korea.

出版信息

Vaccine. 2021 Mar 26;39(13):1870-1876. doi: 10.1016/j.vaccine.2021.01.039. Epub 2021 Feb 26.

Abstract

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12-15 months and 4-6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1-2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4-5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.

摘要

流行性腮腺炎是由腮腺炎病毒引起的传染病。可以使用腮腺炎疫苗预防,该疫苗作为麻疹-腮腺炎-风疹(MMR)疫苗接种。自 1997 年以来,韩国为 12-15 个月和 4-6 岁的儿童接种了这种疫苗,以进行第一和第二剂免疫接种。然而,全世界接种疫苗的人群仍会发生腮腺炎暴发。因此,这些疾病的免疫力可能减弱,或者目前可用的疫苗株与循环野毒株之间存在抗原差异。在韩国引入国家免疫计划后,腮腺炎病例变得零星出现。自 1998 年以来,已出现病毒基因型 F、H 和 I,而疫苗株属于基因型 A。在这里,我们比较了野毒株和腮腺炎疫苗的血凝素神经氨酸酶(HN)基因的氨基酸序列,并测量了它们之间的交叉中和效价。我们选择了 1998 年至 2016 年在韩国流行的 F、H 和 I 型野生腮腺炎毒株,并分析了 HN 基因编码蛋白的氨基酸序列变化。我们测量了韩国分离株和 50 名 1-2 岁儿童血清中的腮腺炎病毒特异性 IgG 和快速焦点减少中和试验(FRNT)效价,这些儿童已接种了一剂 MMR 疫苗。对 HN 蛋白序列的分析显示,糖基化位点没有变化,但在韩国分离株和基因型 A 疫苗株的 HN 蛋白的中和表位位点上,发现了 4-5 个差异。接种疫苗后,针对基因型 F、H 和 I 的 FRNT 效价明显低于针对基因型 A 的效价。这一发现突出表明,根据 HN 基因的遗传保守程度,接种疫苗人群中可能会再次发生腮腺炎暴发。需要进一步研究这一问题,以防止腮腺炎的再次流行。

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