Cross-Protection of Hepatitis B Vaccination among Different Genotypes

Abstract

Hepatitis B (HB) vaccination is the most effective method for preventing HB virus (HBV) infection. Universal HB vaccination containing recombinant HB surface antigens (HBsAg) is recommended. Our data revealed that human monoclonal HB surface antibody (anti-HBs) from individuals inoculated with genotype C-based HB vaccine induced cross-protection against HBV genotype A infection. An in vitro infection model demonstrated anti-HBs-positive sera from individuals inoculated with genotype A- or C-based HB vaccine harbored polyclonal anti-HBs that could bind to non-vaccinated genotype HBV. However, because there were low titers of anti-HBs specific for HBsAg of non-vaccinated genotype, high anti-HBs titers would be required to prevent non-vaccinated genotype HBV infection. Clinically, the 2015 Centers for Disease Control and Prevention guidelines state that periodic monitoring of anti-HBs levels after routine HB vaccination is not needed and that booster doses of HB vaccine are not recommended. However, the American Red Cross suggests that HB-vaccine-induced immune memory might be limited; although HB vaccination can prevent clinical liver injury (hepatitis), subclinical HBV infections of non-vaccinated genotypes resulting in detectable HB core antibody could not be completely prevented. Therefore, monitoring anti-HBs levels after routine vaccination might be necessary for certain subjects in high-risk groups.

Keywords: genotypes; hepatitis B virus; universal vaccination; vaccine escape mutants.

Figure 1

HBV infection protection test using chimeric mice. (a) HBV infection protection test using anti-HBs derived from genotype C HBV in chimeric mice. Chimeric mice were inoculated with these culture supernatants to obtain monoclonal and intact infectious virions. After establishing viremia in these mice, the sera were collected and used as inocula after titration in another experimental chimeric mouse. Five weeks after injection, serum HBV DNA was measured by quantitative PCR. (b) Protection rate against HBV infection in chimeric mice. Antibodies derived from genotype C HBV prevented genotype A infection. HB0478 antibody prevented infection by a vaccine escape mutant. When the titer of anti-HBs is high, it is thought that anti-HBs derived from any genotype HBV can prevent HBV infection. Abbreviations: HBV, hepatitis B virus; anti-HBs, hepatitis B surface antibody; PCR, polymerase chain reaction; HB, hepatitis B.

Figure 2

Sequence of the S-region “a” determinant. Neutralizing (protective) antibodies induced by vaccination target the conformational epitope of the “a” determinant, which is located in the S-region and retains many amino acids including Cys but with some mutations. The second hydrophilic loop (139 to 147 or 149 aa) is the major target for neutralizing anti-HBs produced following natural infection or vaccination. Abbreviations: Cys, cysteine; aa, amino acid; anti-HBs, hepatitis B surface antibody.