Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States

N Engl J Med. 1980 Oct 9;303(15):833-41. doi: 10.1056/NEJM198010093031501.


We assessed the efficacy of an inactivated hepatitis B vaccine in a placebo-controlled, randomized, double-blind trial in 1083 homosexual men known to be at high risk for hepatitis B virus infection. The vaccine was found to be safe and the incidence of side effects was low. Within two months, 77% of the vaccinated persons had high levels of antibody against the hepatitis B surface antigen. This rate increased to 96% after the booster dose and remained essentially unchanged for the duration of the trial. For the first 18 months of follow-up, hepatitis B or subclinical infection developed in only 1.4 to 3.4% of the vaccine recipients as compared with 18 to 27% of placebo recipients (P < 0.0001). The reduction of incidence in the vaccinees was as high as 92.3%; none of the vaccinees with a detectable immune response to the vaccine had clinical hepatitis B or asymptomatic antigenemia. A significant reduction of incidence was already seen within 75 days after randomization; this observation suggests that the vaccine may be efficacious even when given after exposure.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Clinical Trials as Topic
  • Double-Blind Method
  • Hepatitis A / epidemiology
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / analysis
  • Hepatitis B Surface Antigens / immunology*
  • Homosexuality
  • Humans
  • Male
  • Random Allocation
  • United States
  • Vaccination / adverse effects
  • Viral Vaccines / adverse effects
  • Viral Vaccines / standards*


  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Viral Vaccines