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The human immune response to hepatitis B surface antigen

C A Alper1

  • 1Center for Blood Research, Harvard Medical School, Boston, Mass 02115, USA.

Experimental and Clinical Immunogenetics
|January 1, 1995
PubMed
Summary

Hepatitis B vaccination response varies, with some individuals showing poor or no antibody production. Genetic factors, specifically Human Leukocyte Antigen (HLA) haplotypes, significantly influence this immune response, with nonresponse appearing to be recessive.

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Area of Science:

  • Immunology
  • Genetics
  • Vaccinology

Background:

  • The anti-hepatitis B surface antibody (anti-HBs) response exhibits bimodality in healthy individuals.
  • A significant percentage of the population are nonresponders or hyporesponders to the hepatitis B vaccine.

Purpose of the Study:

  • To investigate the genetic basis of nonresponse to hepatitis B vaccination.
  • To elucidate the immunological mechanisms underlying the variable anti-HBs antibody response.

Main Methods:

  • Analysis of extended Human Leukocyte Antigen (HLA) haplotypes in nonresponders.
  • Prospective immunization studies in homozygotes and heterozygotes for specific HLA haplotypes.
  • In vitro studies assessing T-cell proliferation in response to hepatitis B surface antigen (HBsAg) and peptides.

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  • Cellular assays involving antigen-presenting cells and T cells from MHC-identical discordant pairs.

    • Main Results:

    • Two extended haplotypes, [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7], were enriched in nonresponders, suggesting recessive inheritance.
    • Homozygotes for [HLA-B8, SC01, DR3] showed a diminished antibody response compared to heterozygotes.
    • Nonresponders failed to exhibit T-cell lymphoproliferation to HBsAg or an immunodominant nonapeptide.
    • The defect in nonresponse was localized to T cells, not antigen-presenting cells, excluding issues with MHC binding or antigen processing.

    Conclusions:

    • The anti-HBs immune response is linked to the Major Histocompatibility Complex (MHC) and exhibits dominant inheritance.
    • Nonresponse to hepatitis B vaccination is recessive and primarily due to a defect in T-cell function.
    • Understanding these genetic and cellular factors can inform strategies for improving vaccine efficacy in nonresponding populations.