What to do if staff completed Hepatitis B (Hep B) vaccine series but has a negative antibody titer?

From the Guidelines

If a staff member has completed the hepatitis B vaccine series but their titer shows they are negative for antibodies (non-immune), they should receive a second complete hepatitis B vaccine series, as recommended by the most recent and highest quality study 1. This approach is based on the guidelines for the prevention of hepatitis B virus infection in the United States, which suggest that individuals with anti-HBs concentrations of <10 mIU/mL after the primary vaccine series should be revaccinated 1. The second series consists of three additional doses given on a 0,1, and 6 month schedule, followed by anti-HBs testing 1-2 months after the final dose 1. If the titer remains negative after two complete series, the individual is considered a "non-responder" but is still considered protected against hepatitis B surface antigen infection, and no further doses are recommended at that point 1. Healthcare workers who are non-responders should be counseled about precautions to prevent HBV infection and the need for hepatitis B immune globulin prophylaxis if they have a known or probable exposure to hepatitis B surface antigen-positive blood 1. Some key points to consider include:

• Postvaccination serologic testing should be performed 1-2 months after administration of the final dose of the vaccine series using a method that allows determination of a protective concentration of anti-HBs (≥10 mIU/mL) 1
• Immunocompetent persons have long-term protection and do not need further periodic testing to assess anti-HBs levels 1
• Immunocompromised persons might need annual testing to assess anti-HBs concentrations 1
• Anti-HBs levels of ≥10 mIU/mL are generally considered seroprotective, but different assays have different assay cutoff values based on which reported levels of anti-HBs might vary depending on the assay used 1

From the FDA Drug Label

Antibody titers ≥10 mIU/mL against HBsAg are recognized as conferring protection against hepatitis B. The FDA drug label does not provide direct guidance on what to do if staff completed the Hepatitis B vaccine series but has a negative antibody titer.

From the Research

Staff with Negative Antibody Titer after Hep B Vaccine Series

• If staff have completed the Hepatitis B (Hep B) vaccine series but have a negative antibody titer, the approach to management is not straightforward 2, 3.
• According to a 2016 study, there is no need for regular anti-HBs titer testing or booster vaccination in immunocompetent individuals with anti-HBs ≤ 10 IU/L 2.
• However, another study from 1997 suggests that non-responders to the hepatitis B vaccine may benefit from a fourth or fifth dose, or a new complete course of immunization 3.
• A 2022 case series found that prior non-responders to the standard hepatitis B vaccine may gain protection from hepatitis B with Heplisav-B vaccination 4.
• A 2001 study recommends that non-responders to the primary series may benefit from administration of up to three more doses of vaccine, with 40-70% of initial non-responders showing seroconversion to the new series 5.

Booster Dose Vaccination

• The benefits and harms of booster dose hepatitis B vaccination in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL, are unclear 6.
• A 2016 systematic review found no eligible randomized clinical trials to assess the benefits and harms of booster dose hepatitis B vaccination 6.
• Experts from the US suggest delaying booster doses for at least a decade after vaccination in subjects with normal immune status, while European experts recommend assessing vaccine-induced antibody responses in all subjects and administering booster doses at intervals 3.

Management of Non-Responders

• Non-responders to the hepatitis B vaccine may be at continued risk of infection, and alternative vaccination strategies, such as the use of Heplisav-B, may be considered 4.
• The management of non-responders should be individualized, taking into account the person's immune status, occupation, and other risk factors for hepatitis B infection 3, 5.