A non-responder is a person who:

  • is not infected with hepatitis B virus 
  • has a documented history of an age-appropriate course of hepatitis B vaccine 
  • has a current level of antibody to hepatitis B surface antigen (anti-HBs) of <10 mIU per mL 

People who do not respond to this vaccination course, and in whom chronic hepatitis B virus infection has been excluded, should be offered further doses.

People can receive a single booster dose (4th dose) of vaccine to confirm non-responder status. See Serological testing after hepatitis B vaccination

People who are non-responders after receiving the booster should be tested for hepatitis B virus infection. If negative, they are recommended to receive 2 more doses of hepatitis B vaccine 1 month apart. Count the 4th booster dose as the 1st of the 3 repeat doses. Re-test the person for anti-HBs levels at least 4 weeks after the last dose.

A few small studies have reported that non-responders can achieve seroprotection after receiving high-dose formulations or double-dose administration as the 4th, or subsequent, dose of hepatitis B vaccine. However, no consistent evidence suggests that a higher proportion of people would respond with these higher-dose regimens.27-29

Intradermal vaccination in non-responders

Some small observational studies report that some non-responders may respond to intradermal vaccination against hepatitis B.30-32 These results apply to hepatitis B surface antigen–negative healthcare workers who are non-responders to a 3-dose course of vaccination and to subsequent additional intramuscular doses (≥5 doses in total).

These studies used up to 4 doses of Engerix-B (0.25 mL [5 μg] per dose).30 Younger age and longer duration (≥6 months) since the last intramuscular dose may be associated with a better chance of responding.31 

If a person receives an intradermal dose(s), it is recommended that the anti-HBs levels are measured before each subsequent dose to check for seroconversion. 

Persistent non-responders

Inform persistent non-responders that they are probably not protected against hepatitis B, and should minimise potential exposure.

Also inform them about the need for hepatitis B immunoglobulin within 72 hours of parenteral or mucosal exposure to hepatitis B virus (see Table. Post-exposure prophylaxis for non-immune people exposed to a source that is positive for hepatitis B surface antigen in Public health management).

Page history

Last updated: 
27 September 2021
Last reviewed: 
27 September 2021


antibody to hepatitis B surface antigen