Hepatitis B Vaccination for HBsAg-Negative Adults
All adults aged 19-59 years who are HBsAg-negative should receive the complete hepatitis B vaccine series, regardless of risk factors, and adults ≥60 years with any risk factors should also be vaccinated. 1
Universal Vaccination Recommendations
The Advisory Committee on Immunization Practices (ACIP) now recommends universal hepatitis B vaccination for all adults aged 19-59 years, representing a major shift from previous risk-based approaches that resulted in suboptimal coverage. 1 This universal approach eliminates the need for risk factor screening and disclosure, which historically created barriers to vaccination. 1
Age-Specific Guidelines
- Adults 19-59 years: Universal vaccination recommended for all individuals in this age group 1
- Adults ≥60 years with risk factors: Vaccination is recommended 1
- Adults ≥60 years without known risk factors: Vaccination may be offered at provider discretion 1
The new language for older adults shifts responsibility from patient request to provider offering, ensuring proactive vaccination discussions. 1
Standard Vaccination Schedules
Three-Dose Regimens (Most Common)
For most adults, use the standard 3-dose schedule at 0,1, and 6 months with either Engerix-B (20 μg) or Recombivax HB (10 μg). 2, 3
- Minimum intervals must be strictly observed: 4 weeks between doses 1 and 2,8 weeks between doses 2 and 3, and 16 weeks between doses 1 and 3 2
- Doses given ≤4 days before the minimum interval are considered valid 2
- After dose 1,30-55% achieve protection; after dose 2,75% achieve protection; after dose 3, >90% achieve protection 2
Two-Dose Regimen (Heplisav-B)
Heplisav-B offers a simplified 2-dose schedule at 0 and 1 month for adults ≥18 years, achieving approximately 90% seroprotection. 4, 2
- This schedule provides faster completion and higher immunogenicity compared to traditional vaccines 2
- Do not use in pregnant women, hemodialysis patients, or children due to insufficient safety data 1, 2
Accelerated Schedules for Rapid Protection
When immediate protection is needed (e.g., recent exposure, imminent travel to endemic areas):
- Engerix-B: 0,1,2, and 12 months 2, 3
- Twinrix (combined hepatitis A/B): 0,7, and 21-30 days, followed by a dose at 12 months 2, 5
The accelerated schedule achieves 99% seroprotection by month 3 with Engerix-B. 3
Special Populations Requiring Modified Dosing
Hemodialysis Patients
Use 40 μg doses (2 × 20 μg Engerix-B or Recombivax HB) at 0,1,2, and 6 months for hemodialysis patients, as they respond with lower titers than healthy individuals. 1, 2, 3
- The 4-dose regimen achieves 67% seroprotection with a GMT of 93 mIU/mL 3
- Annual anti-HBs testing is required, with booster doses when levels fall below 10 mIU/mL 2
- Standard adult doses are inadequate for this population 2
Pregnant Women
Use only Engerix-B, Recombivax HB, or Twinrix in pregnant women—never Heplisav-B or PreHevbrio due to insufficient pregnancy safety data. 1, 2
Immunocompromised Adults
Higher doses (40 μg) may be needed for immunocompromised adults, similar to hemodialysis patients. 1, 2
Managing Interrupted Vaccination Series
If the vaccination series is interrupted at any point, never restart the series—simply continue where you left off. 6, 4, 2 This is a critical principle based on immunologic memory, which persists even with extended intervals between doses. 6, 4
- If interrupted after dose 1, give dose 2 as soon as possible, then dose 3 at least 8 weeks after dose 2 and at least 16 weeks after dose 1 6, 2
- Restarting the series wastes vaccine doses and delays protection 6, 2
Pre-Vaccination Testing Considerations
Pre-vaccination testing is not required and should not be a barrier to vaccination, especially in populations that are difficult to reach. 1
However, in settings with high rates of previous HBV infection, pre-vaccination testing (HBsAg, anti-HBs, anti-HBc) performed concomitantly with the first dose may reduce costs by avoiding vaccination of already immune individuals. 1
- Presence of anti-HBs indicates immunity from prior vaccination or infection 1
- Presence of anti-HBc indicates previous or ongoing HBV infection 1
- Lack of testing access should never delay vaccination of susceptible persons 1
Post-Vaccination Serologic Testing
Routine post-vaccination testing is recommended only for specific high-risk groups 1-2 months after the final dose: 4, 2
- Healthcare personnel with occupational blood exposure risk
- Hemodialysis patients
- HIV-infected persons
- Other immunocompromised individuals
- Household or sexual contacts of HBsAg-positive persons
Seroprotection is defined as anti-HBs ≥10 mIU/mL. 6, 2
Management of Non-Responders
For individuals with anti-HBs <10 mIU/mL after completing the series:
- Consider revaccination with Heplisav-B or high-dose Engerix-B 6
- A fourth dose in poor responders aged >50 years achieves 92% response rate versus 63% after three doses 7
- Older adults (>40 years), males, obese individuals, and smokers have higher non-response rates 8, 9
Common Pitfalls to Avoid
- Never restart an interrupted series—this wastes doses and delays protection 6, 4, 2
- Never give the third dose before 16 weeks from the first dose, even if 8 weeks have passed since the second dose 2
- Never use standard adult doses in hemodialysis patients—they require 40 μg doses 1, 2
- Never use Heplisav-B or PreHevbrio in pregnant women, children, or hemodialysis patients 1, 2
- Never require acknowledgment of specific risk factors before vaccinating adults 19-59 years—universal vaccination is now recommended 1
- Never delay vaccination while waiting for serologic testing results in populations difficult to reach 1
Implementation Strategies
In settings where a high proportion of persons have HBV risk factors (STD clinics, drug treatment facilities, correctional facilities), implement standing orders to vaccinate all adults who have not completed the series. 1
In primary care settings, providers should offer vaccination to all adults in recommended age groups without requiring patients to request it or acknowledge specific risk factors. 1