Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission
Abstract Background Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We...
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doaj-cca75bcac9c041d699dfb7914ecf251b2020-11-25T04:03:18ZengBMCBMC Infectious Diseases1471-23342019-11-0119111210.1186/s12879-019-4624-9Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmissionHaruki Komatsu0Ayano Inui1Yasuto Suzuki2Masaya Sugiyama3Tomoo Fujisawa4Department of Pediatrics, Toho University, Sakura Medical CenterDepartment of Pediatric Hepatology and Gastroenterology, Eastern Yokohama HospitalDepartment of Pediatrics, Kushiro Red Cross HospitalResearch Center for Hepatitis and Immunology, National Center for Global Health and MedicineDepartment of Pediatric Hepatology and Gastroenterology, Eastern Yokohama HospitalAbstract Background Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections. Case presentation Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7–2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child. Conclusions VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission.http://link.springer.com/article/10.1186/s12879-019-4624-9Hepatitis B virusImmunoprophylaxisUmbilical cordNailsMutantVariant |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haruki Komatsu Ayano Inui Yasuto Suzuki Masaya Sugiyama Tomoo Fujisawa |
spellingShingle |
Haruki Komatsu Ayano Inui Yasuto Suzuki Masaya Sugiyama Tomoo Fujisawa Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission BMC Infectious Diseases Hepatitis B virus Immunoprophylaxis Umbilical cord Nails Mutant Variant |
author_facet |
Haruki Komatsu Ayano Inui Yasuto Suzuki Masaya Sugiyama Tomoo Fujisawa |
author_sort |
Haruki Komatsu |
title |
Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission |
title_short |
Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission |
title_full |
Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission |
title_fullStr |
Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission |
title_full_unstemmed |
Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission |
title_sort |
deep sequencing of hepatitis b surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child hbv transmission |
publisher |
BMC |
series |
BMC Infectious Diseases |
issn |
1471-2334 |
publishDate |
2019-11-01 |
description |
Abstract Background Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections. Case presentation Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7–2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child. Conclusions VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission. |
topic |
Hepatitis B virus Immunoprophylaxis Umbilical cord Nails Mutant Variant |
url |
http://link.springer.com/article/10.1186/s12879-019-4624-9 |
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