Chronic hepatitis B infection in adolescents vaccinated at birth: An alarm bell in favor of the need for a booster?


  • Potential conflict of interest: Dr. Tozzi received grants from GlaxoSmithKline and Sanofi Pasteur MSD.

To the Editor

Wu et al.[1] reported that a significant proportion of adolescents born to hepatitis B surface antigen (HBsAg)-positive mothers, who had postnatal hepatitis B immune globulin (HBIG) and hepatitis B vaccine, lost immune memory and developed a HBsAg carrier state. Having maternal hepatitis B e antigen (HBeAg) positivity was the most important determinant for developing chronic hepatitis B.

Vaccination has proved to be highly effective in preventing and controlling hepatitis B, carrier rate, and hepatitis B virus (HBV)-related mortality worldwide. Long-term protection studies indicate that vaccine-induced anti-HBs concentrations decline over time, with antibody (Ab) levels falling below the protective threshold (10 mIU/mL) in one third to one half of vaccinees 10-20 years later; however, immunological memory usually persists.[2, 3] This is because Ab maintenance after vaccination depends on the number of long-lived plasma cells, whereas booster response is a function of memory B cells. Evidence indicates that memory B cells effectively respond to antigen challenge even when Ab falls below the protective level.[4] Thus, booster doses are not needed in immunocompetent individuals to maintain long-term protection.

However, failure to develop postbooster anamnestic response has been reported, raising concern that immune memory may wane during the second decade postvaccination.[5, 6] In his study, Wu et al. show that 15% of adolescents born to HBsAg/HBeAg-positive mothers who received primary infantile vaccination developed chronic HBV infection. In addition, one sixth of vaccinees were unable to respond to booster vaccination, having lost immunological memory.

Individuals who lost immunological memory may become vulnerable to HBV infection, especially in highly endemic regions—such as some Asiatic countries—where HBsAg carriers are often positive for HBeAg, then highly infectious. Thus, need for a booster in this setting, where risk of acquiring infection and becoming chronic is high, should be considered. If this were the policy, booster should be given before loss of immunological memory occurs.

  • Luisa Romanò, Ph.D.1

  • Rita Carsetti, M.D.2

  • Alberto E. Tozzi, M.D.3

  • Alfonso Mele, M.D.4

  • Alessandro R. Zanetti, Ph.D.1

  • 1Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy

  • 2Immunology Research Area and Immunological Diagnosis Unit, Bambino Gesù Children's Hospital, Rome, Italy

  • 3Research Area of Multifactorial Diseases and Complex Phenotypes, Bambino Gesù Children's Hospital, Rome, Italy

  • 4National Center of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy