Efficacy of intradermal plus intramuscular Recombinant hepatitis B vaccination in vaccine nonresponders

Ir J Med Sci. 2026 Feb;195(1):243-254. doi: 10.1007/s11845-025-04146-5. Epub 2025 Nov 3.

Abstract

Introduction: We aimed to determine the antibody response of intradermal (ID) plus intramuscular (IM) recombinant hepatitis B vaccination in individuals with inadequate immune response despite vaccination.

Methods: This single-center, retrospective study included individuals aged ≥18 years who had previously completed the primary 3-dose vaccination course for hepatitis B and had anti-HBs titers <10 mlU/ml. Participants were administered a double dose of recombinant hepatitis B vaccine (5 microgram ID+35 microgram IM) at months 0, 1, and 6. Quantitative anti-HBs titers were assessed at months 2 and 7. Vaccination response was categorized as unresponsive (anti-HBs<10 mlU/ml), weak (anti-HBs=10-100 mlU/ml), moderate (anti-HBs=101-1000 mlU/ml), and strong (anti-HBs>1000 mlU/ml).

Results: A total of 43 individuals were included. After the 2nd and 3rd doses of vaccination, protective antibody responses (anti-HBs>10 mlU/ml) were obtained 81.3% (27.9% weak response, 16.3% moderate response, 37.2% strong response) and 93% (16.3% weak response, 27.9% moderate response, 48.8% strong response), respectively. Anti-HBs antibody titers increased from 505±501 in the 2nd vaccination to 666±469 in the 3rd vaccination (p=0.003). After the 3rd dose of vaccination, protective antibody responses inreased from 86.7% to 100% in PLwHIV, from 69.2% to 76.9% in patients with rheumatic diseases, and from 91.7% to 100% in immunocompetent individuals compared to the second dose of vaccination. No antibody response was achieved in any of the patients using rituximab.

Conclusion: ID (5 µg) plus IM (35 µg) recombinant hepatitis B vaccine is promising as an alternative vaccination method in various specific populations, which unresponsive to standard vaccination, such as PLwHIV, immunocompetent patients, and immunomodulator users.

Keywords: Antibody responses; Hepatitis B; Intradermal; Intramusculer; Vaccination.

MeSH terms

  • Adult
  • Female
  • Hepatitis B Antibodies / blood
  • Hepatitis B Vaccines* / administration & dosage
  • Hepatitis B Vaccines* / immunology
  • Hepatitis B* / immunology
  • Hepatitis B* / prevention & control
  • Humans
  • Injections, Intradermal
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Retrospective Studies
  • Vaccination / methods
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Young Adult

Substances

  • Hepatitis B Vaccines
  • Hepatitis B Antibodies
  • Vaccines, Synthetic