Skip Navigation LinksSkip Navigation Links
Centers for Disease Control and Prevention
Safer Healthier People
Blue White
Blue White
bottom curve
CDC Home Search Health Topics A-Z spacer spacer
Blue curve MMWR spacer

Epidemiologic Notes and Reports Suboptimal Response to Hepatitis B Vaccine Given by Injection into the Buttock

Hepatitis B (HB) vaccine was licensed in November 1981 as a highly immunogenic and effective vaccine against hepatitis B virus (HBV) infection. Large studies before licensure demonstrated, with one exception, that the vaccine induced antibody* in over 90% of healthy adult recipients of the three-dose series (1-3). The one exception, in which only 85% of recipients responded to vaccination, was later shown to be caused by partial freezing of the vaccine during shipment (4).

Since vaccine licensure, however, the vaccine manufacturer (Merck, Sharp & Dohme) and CDC have received reports of suboptimal response to vaccine in the health-care personnel of a number of hospitals and other vaccine users. Two such examples, in which only 82% and 68% of normal adults responded to vaccination, have recently been published (5-6). Initial investigations of these and other reports by the manufacturer and by CDC included site visits, repeat serologic testing of vaccine recipients to confirm poor response, assays of residual vaccine for evidence of freezing and for retention of potency, and review of vaccine lots used. These investigations generally confirmed suboptimal vaccine response but failed to identify any specific cause. The investigations did indicate that, in many such instances, vaccine had been given by buttock (gluteal) injection, in contrast to the arm (deltoid) injection used in all prelicensure vaccine studies.

Two recent investigations, one by the vaccine manufacturer and the other by CDC, indicate that site of vaccine injection is important in explaining suboptimal response to vaccine in many vaccine programs. Both studies were retrospective telephone surveys of hospitals or hemodialysis units that had vaccinated and then serotested significant numbers of persons after vaccination.

Vaccine manufacturer's study: In December 1984, the vaccine manufacturer surveyed two groups of vaccine users: over 90 hospitals that had contacted the manufacturer reporting suboptimal vaccine response and an additional 12 hospitals known to have conducted large vaccination programs and to have done postvaccination testing. The telephone survey verified the exact number of persons completing vaccination and the number failing to respond to vaccine and determined the vaccine injection site. Injection site for the hospital was classified as arm if over 90% of persons received vaccine in the arm; buttock if over 90% received vaccine in the buttock; and mixed for all others.

In both surveys, vaccine response rate was significantly higher in hospitals using arm injection than in those using buttock injection (Table 1). Among hospitals that reported suboptimal vaccine response, the pooled response rate for vaccinees was 88% in hospitals using arm injection and 73% in those using buttock injection (p 0.01). Among the 12 other hospitals, response rates were higher, as would be expected for hospitals not selected for poor vaccine response; however, response to arm injection was higher than for buttock injection. Furthermore, when 55 hospitals that had vaccinated and tested 50 or more persons were ranked by response rate to vaccine and compared, arm injection was clearly superior (Figure 1). Among 18 institutions reporting 90% or better response, 13 used arm injection, and one used buttock. Among 21 reporting lower than 80% response, 18 used buttock injection, and two used arm injection.

CDC's study: To avoid selection bias inherent in the above study and to more accurately assess vaccine response in a representative group of vaccine users, in January 1985, CDC's Hepatitis Branch assessed vaccine response among staff in all hemodialysis units known to have vaccinated 20 or more staff as of December 1983. Sixty-three centers were contacted and interviewed, and 57 were included in the final data. Among six centers not included, one refused to participate; two did not do postvaccination testing; two tested only a small sample of vaccinees; and one had participated in a prelicensure vaccine trial. In addition to the questions in the first survey, centers were asked to identify the laboratory method of postvaccination testing, length of needle used for injection, and proportions of vaccinees who were over 40 years of age or who were significantly overweight. Among the 57 centers, 20 used arm injection (as defined above); 23 used buttock injection; and 14 used mixed sites of injection.

Antibody response was significantly higher in centers using the arm as the injection site (Table 2). The average vaccine response in such centers was 93%, compared with 82% response in sites using buttock injection (p 0.01). This difference remained highly significant when the method of postvaccination testing and the proportions of vaccinees who were over 40 years old or overweight were considered in the analysis. Despite overall poorer response with buttock injection, response in individual centers varied widely (Figure 1). Among centers using buttock injection, eight (35%) reported excellent response to vaccine (over 90% responding), and nine (39%) reported poor response rates (fewer than 80% responding). In contrast, 75% of centers using arm injection reported excellent response, and only one (5%) reported poor response. Seventeen centers using the buttock as injection site reported using 1 1/2-inch needles, while the other six used 1-inch needles. There was no difference in response rates among these two groups. Reported by AA McLean, HA Guess, EM Scolnick, Merck, Sharp & Dohme, West Point, Pennsylvania; Hepatitis Br, Div of Viral Diseases, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Although these studies are preliminary, they strongly suggest that response to HB vaccine is higher when vaccine is given in the arm than in the buttock. Furthermore, they appear to provide an explanation for poor rates of response to HB vaccine reported in some vaccine programs. These data are the first to indicate that response to any inactivated vaccine given intramuscularly to adults may vary with injection site. The Immunization Practices Advisory Committee (ACIP) has previously recommended that the arm is the preferred site of injection for all adult vaccines (7). However, the present studies demonstrate that the buttock is a commonly used site for HB vaccination. Because of the important implications for use of HB vaccine and other killed vaccines, a prospective study has been initiated to confirm these data.

The physiologic reasons for lower response rate to vaccine injections in the buttock are yet to be defined. The most likely explanation is that injections given in the buttock frequently fail to reach muscle and are instead deposited in fat where the vaccine may not be well mobilized. The authors of a recent study using CAT scans to assess gluteal fat thickness estimated that, when adults are given injections in the buttock using a 3.5-cm (1-3/8-inch) needle, 85% of injections in men and 95% of those in women are deposited in fat rather than muscle (8). An earlier study showed that lidocaine is mobilized more slowly when injected in the buttock than when given in the arm (9).

Pending further data, the ACIP and CDC recommend that the arm be used as the site of HB vaccine administration in all adults. For hemodialysis patients, who do not respond as well to vaccine as immunocompetent individuals, vaccine should be given in the arm unless this will jeopardize shunt access. For infants born to HBV-carrier mothers, the preferred site for HB vaccination remains the anterolateral thigh.


  1. Krugman S, Holley HP Jr, Davidson M, Simberkoff MS, Matsaniotis N. Immunogenic effect of inactivated hepatitis B vaccine: comparison of 20 microgram and 40 microgram doses. J Med Virol 1981;8:119-21.

  2. Szmuness W, Stevens CE, Harley EJ, et al. 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;303:833-41.

  3. Francis DP, Hadler SC, Thompson SE, et al. The prevention of hepatitis B with vaccine. Report of the Centers for Disease Control multi-center efficacy trial among homosexual men. Ann Intern Med 1982:97:362-6.

  4. McLean AA, Shaw R Jr. Hepatitis B vaccine (Letter). Ann Intern Med 1982;97:451.

  5. Strickler AC, Kibsey PC, Vellend H. Seroconversion rates with hepatitis B vaccine (Letter). Ann Intern Med 1984;101:564.

  6. Schaaff DM, Lender M, Snedeker P, Graham LA. Hepatitis B vaccine in a hospital. Ann Intern Med 1984;101:720-1.

  7. CDC. General recommendations on immunization. MMWR 1983;32:1-16.

  8. Cockshott WP, Thompson GT, Howlett LJ, Seeley ET. Intramuscular or intralipomatous injections? N Engl J Med 1982;307:356-8.

  9. Cohen LS, Rosenthal JE, Horner DW Jr, et al. Plasma levels of lidocaine after intramuscular administration. Am J Cardiol 1972;29:520-3.

Disclaimer   All MMWR HTML documents published before January 1993 are electronic conversions from ASCII text into HTML. This conversion may have resulted in character translation or format errors in the HTML version. Users should not rely on this HTML document, but are referred to the original MMWR paper copy for the official text, figures, and tables. An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S. Government Printing Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800. Contact GPO for current prices.

**Questions or messages regarding errors in formatting should be addressed to

Page converted: 08/05/98


Safer, Healthier People

Morbidity and Mortality Weekly Report
Centers for Disease Control and Prevention
1600 Clifton Rd, MailStop E-90, Atlanta, GA 30333, U.S.A


Department of Health
and Human Services

This page last reviewed 5/2/01