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Evaluation of the effect of hepatitis B vaccines derived from different genotypes of hepatitis B viruses

Not Applicable
Conditions
Infection of hepatitis B virus
Registration Number
JPRN-UMIN000014363
Lead Sponsor
St. Marianna University, School of Medicine
Brief Summary

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, rho=0.989; gtC-sera, rho=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.

Detailed Description

Not available

Recruitment & Eligibility

Status
Complete: follow-up complete
Sex
All
Target Recruitment
150
Inclusion Criteria

Not provided

Exclusion Criteria

Informed consents were not obtained. Sufficient amount of serum was not obtained after their medical examinations.

Study & Design

Study Type
Observational
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To detect cross-reaction of HBs antibodies in HB vaccine-immunized sera to HBs antigens from different HBV genotypes by ELISA.
Secondary Outcome Measures
NameTimeMethod
To examine whether anti-HBs antibodies generated by HB vaccination protect the infection of HBV whose genotype is different from that of the immunized vaccine.
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