676 Immunogenicity of an Inactivated Hepatitis A Vaccine in Alaska Native Children and Native and Non-Native Adults Brian J. McMahon, James Williams, Lisa Bulkow, Mary Snowball, Robert Wainwright, Margaret Kennedy, and David Krause Alaska Native Medical Center. Alaska Area Native Health Services, Indian Health Service. and Arctic Investigations Program, National Center for Infectious Diseases. Cenrers for Disease Conrrol and Prevention. Anchorage. Alaska; SmithKline Beecham Pharmaceuticals. King of Prussia. Penns.vlvania The response to an inactivated hepatitis A vaccine was assessed in 307 persons: 163 Alaska Native children, ages 3-6 years, and 144 Native (84) and non-Native (60) adults. All adults received the same vaccine schedule (0, 1, and 12 months), whereas children were randomized to receive three different schedules (0, 1, and 6; 0, 1, and 2; or 0, 1, and 12 months). After one dose, 141 (96%) of 147 children and 129 (90%) of 143 adults responded with levels of antibody to hepatitis A virus >20 mIU/mL. After three doses, all participants responded. The geometric mean titer (GMT) 1 month after the third dose was significantly higher in children who received the third dose 12 months after the first dose rather than 2 months after the first dose. While there were differences in the GMT of some blood samples by age, sex, and ethnicity, all participants responded to the vaccine. Hepatitis A virus (HAV) infection is an important world- wide problem. In Alaska, large HAV epidemics occur every IO- 12 years, resulting in thousands of cases of clinical illness and a few deaths [ 11. Inactivated HAV vaccines have been developed by purification of virus obtained by propagation of HAV in tissue culture with human diploid fibroblasts [2- 4]. Studies in volunteers have shown the vaccine to have a high degree of safety and immunogenicity [4-IO]. Recently, the efficacy ofthese inactivated HAV vaccines has been dem- onstrated in controlled trials [ 11, 121. Studies have com- pared different dosing schedules in adults, but there is little information about vaccine schedules in children. We used an inactivated HAV vaccine to compare three vaccine dosing schedules in children and one schedule in adults and to determine if there were any differences in re- sponse by age, sex, or ethnicity in 307 Alaska Native and non-Native volunteers. Received I I July 1994: revised 30 September 1994. Presented in part: International Symposium on Viral Hepatitis and Liver Disease, Tokyo, lo- I4 May I993 (abstract 036). Informed consent was obtained from all patients (adults) or their parents (children). The human experimentation guidelines of the Indian Health Service, US Public Health Service, were followed in the conduct of this study. The study was approved by the Alaska Area Native Health Service Research and Publications Committee and the Anchorage Native Health Board. The opinions expressed are those of the authors and do not necessarily reflect the views of the Indian Health Service. Use ofbrand names is for identification only and does not imply endorse- ment by the US Public Health Service or the Department of Health and Human Services. D.K. is an employee of SmithKline Beecham. Grant support: SmithKline Beecham Biologics. Reprints or correspondence: Dr. Brian J. McMahon. Dept. of Medicine, Alaska Native Medical Center, 255 Gambell, Anchorage, AK 99501. The Journal of Infectious Diseases 1995;171:676-9 0 1995 by The University of Chicago. All rights reserved. 0022- I899/95/7 103-0022$01 .OO Materials and Methods Participants were screened for antibody to HAV (anti-HAV) IgG. Three groups of persons seronegative for anti-HAV 1gG were recruited for the study: 163 Alaska Native children ages 3-6 years, 84 Alaska Native adults 2 18 years old, and 60 Cau- casian adults 220 years old. The hepatitis A vaccine used (Havrix; SmithKline Beecham Biologicals, Rixensart, Belgium) is a formalin-inactivated vac- cine prepared from HAV strain HM-I 75 [3]. Seronegative children were randomized to receive one of three vaccine schedules: 360 ELISA units (EU) of vaccine (0.5 mL) at 0. 1, and 2 months; 0, 1, and 6 months; or 0, 1, and 12 months. Seronegative adults received 720 EU of vaccine ( 1 mL) at 0, 1, and 12 months. All inoculations were administered intra- muscularly deep in the deltoid muscle. Laboratory testing for prevaccination anti-HAV IgG was done by RIA (HAVAB; Abbott Laboratories, Abbott Park, IL) at the laboratories ofthe Arctic Investigations Program. Postvac- cination testing was done in blinded fashion in Rixensart by an ELISA for total immunoglobulin. This test is an inhibition assay in which the HAV-specific antibodies present in the test serum sample inhibit the binding of an enzyme-labeled anti-HAV to HAV antigen captured by anti-HAV immunoglobulin coated on a microtiter plate [3]. The results are quantitative and expressed in milliinterna- tional units. Sera were divided into batches, and internal con- trols were included with each batch run for validation purposes. This assay has a sensitivity for detecting anti-HAV of 20 mIU/ mL, which correlated with seroconversion in previous studies [3, 6, 71. Serum specimens were obtained for anti-HAV testing be- fore vaccination and 1 month after each dose was administered. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured for all participants at each visit. Persons with ALT or AST > 1.5 times the upper limit of normal were excluded. All participants were given diary cards on which to record any adverse event for 3 days after each inoculation. In addition,