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Eur J Clin Microbiol Infect Dis. 2018 Jun;37(6):1153-1162. doi: 10.1007/s10096-018-3235-5. Epub 2018 Apr 8.

Quasispecies characters of hepatitis B virus in immunoprophylaxis failure infants.

Author information

1
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
2
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China.
3
Department of Infectious Disease, The Fifth People's Hospital of Chongqing, Chongqing, People's Republic of China.
4
Clinical laboratory, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
5
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China. ahuang1964@163.com.
6
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China. ahuang1964@163.com.
7
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China. longquanxin@gmail.com.
8
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People's Republic of China. longquanxin@gmail.com.

Abstract

Hepatitis B vaccination prevents 80-95% of transmission and reduces the incidence of HBV in children. The variations in the a determinant of HBV surface antigen (HBsAg) have been reported to be the most prevalent cause for vaccine or antibody escape. There is a conflicting evidence on as to whether escape mutants arise de novo in infected infants or whether the mutants, that have preexisted maternally, subsequently undergo selective replication in the infant under immune pressure. Here, we report that nearly 65% (55 of 85) vaccination failure in child patients has no amino acid substitution in a determinant as seen by Sanger sequencing. We further employed an Illumina sequencing platform-based method to detect HBV quasispecies in four immunoprophylaxis failure infants and their mothers. In our data, the substitution rate of amino acid located at a determinant is relatively low (< 10%), I/T126A, C124S, F134Y, K141Q, Q129H, D144A, G145V, and N146K, which showed no statistical difference to their mothers, proving that these vaccine escape mutants preexist maternally as minor variants. Besides that, bioinformatical analysis showed that the binding affinity of high variation epitopes (amino acid divergence in mother and their infants > 20%) to related HLA molecules was generally decreased, these traces of immune escape suggesting that immune pressure was present and was effective in all samples.

KEYWORDS:

Hepatitis B virus; Immunoprophylaxis failure infants; Ultra-deep sequencing; a determinant substitution

PMID:
29629487
DOI:
10.1007/s10096-018-3235-5
[Indexed for MEDLINE]

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