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Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

In universal hepatitis B (HB) vaccination, single vaccine-derived polyclonal anti-HBs antibodies (anti-HBs) need to inhibit infection of HB viruses (HBV) of non-vaccine genotypes. We experimentally addressed this issue.

Methods

Anti-HBs-positive sera were obtained by vaccination with genotype A- or C-derived HBs antigen (HBsAg, gtA-sera or gtC-sera). Their reactivity to genotype A- and C-derived HBsAg (gtA-Ag and gtC-Ag) was measured by ELISA. The capacity of sera to neutralize HBV was evaluated using an in vitro infection model.

Results

Of 135 anti-gtA-Ag-reactive gtA-sera, 134 (99.3%) were anti-gtC-Ag-reactive. All (100%) 120 anti-gtC-Ag-reactive gtC-sera were anti-gtA-Ag-reactive. The reactivity to gtA-Ag was strongly correlated with that to gtC-Ag (gtA-sera, ρ = 0.989; gtC-sera, ρ = 0.953; p < 0.01). In gtA-sera (n = 10), anti-HBs to gtA-Ag were less completely absorbed with gtC-Ag (96.4%) than with gtA-Ag (100%, p < 0.05). Similarly, in gtC-sera (n = 10), anti-HBs to gtC-Ag were less completely absorbed with gtA-Ag (96.0%) than with gtC-Ag (100%, p < 0.01). Thus, 3.6 and 4.0% of anti-HBs in gtA-sera and gtC-sera were vaccine genotype HBsAg-specific, respectively. In the neutralization test, gtA-sera (n = 4) and gtC-sera (n = 3) with anti-HBs titers adjusted to 100 mIU/mL equally inhibited genotype C HBV infection (92.8 vs. 95.4%, p = 0.44). However, at 30 mIU/mL, the gtA-sera less effectively inhibited infection than the gtC-sera (60.2 vs. 90.2%, p < 0.05).

Conclusions

Vaccination with genotype A- or C-derived HBsAg provided polyclonal anti-HBs that sufficiently bound to non-vaccine genotype HBsAg. However, a small portion of anti-HBs were specific to the vaccine genotype HBsAg. High anti-HBs titers would be required to prevent HBV infection of non-vaccine genotypes. UMIN/CTR UMIN000014363.

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Abbreviations

Anti-HBs:

Anti-hepatitis B surface antibodies

DNA:

Deoxyribonucleic acid

ELISA:

Enzyme-linked immunosorbent assay

F:

Female

HB:

Hepatitis B

HBIG:

Immunoglobulins containing high-titer antibodies against HBsAg

HBsAg:

Hepatitis B surface antigen

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

gtA-Ag:

Genotype A-derived hepatitis B surface antigen

gtC-Ag:

Genotype C-derived hepatitis B surface antigen

gtA-sera:

Anti-HBs-antibody-positive sera from Heptavax-II-immunized individuals

gtC-sera:

Anti-HBs-antibody-positive sera from Bimmugen-immunized individuals

M:

Male

NC:

Negative control

NI-sera:

Anti-HBs-negative sera from HB vaccine-non-immunized individuals

OD:

Optical density

PCR:

Polymerase chain reaction

SD:

Standard deviation

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Acknowledgements

The authors are indebted to Ms Atsuko Nozawa and Ms Fumiko Oikawa for their technical assistance. The authors are also grateful to Kaketsuken, Abbott, Siemens, Abcam, and Thermo Fisher Scientific for their support for this study. This work was partly supported by a Grant from Ministry of Health, Labour and Welfare.

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Authors and Affiliations

  1. Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, 2-16-1, Sugao, Miyamae-Ku, Kawasaki, 216-8511, Japan

    Masaki Kato & Manae Suzuki Kurokawa

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Masaki Kato, Nobuyuki Matsumoto & Fumio Itoh

  3. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Susumu Hamada-Tsutsumi & Yasuhito Tanaka

  4. Division of Gastroenterology and Hepatology, Kawasaki Municipal Tama Hospital, Kawasaki, Japan

    Chiaki Okuse

  5. Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

    Aiko Sakai & Ryo Sumazaki

  6. Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan

    Masaaki Sato, Toshiyuki Sato, Mitsumi Arito, Kazuki Omoteyama, Naoya Suematsu, Kazuki Okamoto & Tomohiro Kato

  7. Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan

    Takanobu Kato

  8. Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Hiroshi Yotsuyanagi

Authors
  1. Masaki Kato
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  2. Susumu Hamada-Tsutsumi
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  3. Chiaki Okuse
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  6. Masaaki Sato
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  12. Takanobu Kato
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  17. Tomohiro Kato
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  18. Manae Suzuki Kurokawa
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Corresponding author

Correspondence to Manae Suzuki Kurokawa.

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Conflict of interest

Chiaki Okuse received a research grant from Takeda Pharma. Yasuhito Tanaka received lecture fees from Chugai Pharma, Bristol-Myers Squibb, and GlaxoSmithKline. Hiroshi Yotsuyanagi received lecture fees from MSD K.K. and Bristol-Myers Squibb. Tomohiro Kato received a research grant from FUJI OIL.

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Kato, M., Hamada-Tsutsumi, S., Okuse, C. et al. Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes. J Gastroenterol 52, 1051–1063 (2017). https://doi.org/10.1007/s00535-017-1316-3

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  • DOI: https://doi.org/10.1007/s00535-017-1316-3

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