Immunogenicity of a yeast-recombinant hepatitis B vaccine in high-risk children

Horizontal transmission of hepatitis B virus (HBV) from illicit drug users to their contacts, including young children, can be prevented by active immunization against HBV. Yeast-recombinant hepatitis B vaccines are now available for this purpose, but their potential efficacy in such high-risk contacts has not yet been evaluated. Therefore we gave 20 mcg of a recombinant yeast-derived hepatitis B vaccine to 38 children who were at high risk for HBV infection because they had been institutionalized in a community for drug users in which 8.7% of the occupants are carriers. After third dose of vaccine (at 0, 1, and 6 months), all children had anti-HBs responses with titers of 10 mIU/ml or more, with 81% showing responses greater than 1,000 mIU/ml. At 12 months, the percentage of anti-HBs-positive children was 100%, and the percentage of children with anti-HBs higher than 1,000 mIU/ml was 56%. None of the children developed HBV infection during follow-up. Hence the recombinant vaccine was immunogenic, with percentages of seroconversion and anti-HBs titers comparable with those attained in other categories of high-risk children with plasma-derived vaccines.     

Comparison of the immunogenicity of reduced doses of two recombinant DNA hepatitis B vaccines in New Zealand children

A group of 201 hepatitis B virus (HBV) sero-negative children 1-12 years of age received either three 2 micrograms doses of Merck Sharp and Dohme (MSD) or Smith Kline and French (SKF) recombinant DNA (rDNA) hepatitis B vaccine I.M. at monthly intervals. Each recipient was tested 4-6 weeks later for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay (EIA) and radioimmunoassay (RIA). Ninety-six 4-5-year-old children, given 2 micrograms doses of a plasma-derived vaccine (MSD, H-B-Vax) I.M. at 0, 1, 2 months, were tested at the same time with the same assays for comparison. Anti-HBs responses and geometric mean titres (GMT) were significantly higher with the MSDrDNA vaccine (96% and 338.9 IU/liter) than with the SKF/r DNA vaccine (82.3% and 69.4 IU/liter). We conclude that for the protection of young children, 2 micrograms doses of the MSD rDNA hepatitis B vaccine may be used under similar circumstances in which 2 micrograms of the MSD plasma-derived vaccine was used. Further studies are needed before the other rDNA hepatitis B vaccine may be used in lower than the 10 micrograms dose recommended in children.     

Immunogenicity of hepatitis B vaccine simultaneously administered with the expanded programme on immunisation (EPI)

To assess the immunogenicity of hepatitis B vaccine simultaneously administered with the Expanded Programme on Immunisation (EPI) vaccines, a total of 300 consecutive infants, ranging in age between 6 weeks and 6 months, were alternatively assigned to the revised EPI and to EPI plus plasma-derived hepatitis B vaccine (Hevac B Pasteur). Four dosages (2 mcg or 0.5 ml each) of hepatitis B vaccine were given intramuscularly. HBsAg, anti-HBc, and anti-HBs were determined at day 0 and at day 210 in both groups by radioimmunoassay methods. The anti-HBs titre levels and geometric mean titres (GMTs) were determined at day 180 and day 210. There were three new hepatitis B virus infections in the control group and none in the study group by day 210. The seroconversion rates in the study group were 66% at day 180 and 84% at day 210, the respective GMTs being 116 and 940. Although the duration of observation is short (7 months) and the difference in the rate of infection between the two groups is not statistically significant (P greater than 0.05), the immunogenicity of the vaccine appears to be good. The simultaneous administration of hepatitis B vaccine and the EPI vaccines is logistically ideal. However, we suggest a further study using a larger dose of the Hevac B Pasteur vaccine to find out if a higher seroconversion rate than the 84% observed in this study could be achieved.     

Safety and immunogenicity of a recombinant hepatitis B vaccine

A hepatitis B vaccine produced in yeast by recombinant DNA technology was evaluated using 5-micrograms and 10-micrograms doses in a randomized trial lasting 7 months in 110 male armed forces recruits aged 17-19 years. Results were compared to those of an identical trial of a plasma-derived vaccine. No allergic reactions were observed, and the rate of mild side effects was similar to the plasma-derived vaccine. Seroconversion rates in the first month were 60% (33/55) and 67% (37/55) with the 5-micrograms and 10-micrograms doses of the recombinant vaccine, respectively. All participants seroconverted by 3 months, and none lost antibody. These results are very similar to those for plasma-derived vaccine. Comparison of titres of antibody to hepatitis B surface antigen (anti-HBs) showed a slightly higher level with the 10-micrograms than with the 5-micrograms dose of the recombinant vaccine. Geometric mean titres of anti-HBs after the booster dose were similar in the 5-micrograms and 10-micrograms dose recombinant vaccine groups (2,620 and 2,748 IU/l, respectively) and in the 5-micrograms plasma-derived vaccine group (3,591 IU/l) but significantly higher (9,227 IU/l) with the 10-micrograms dose of the plasma-derived vaccine. These results confirm the safety and immunogenicity of the recombinant vaccine, although further study is needed on the duration of immunity.     

Recombinant hepatitis B triple antigen vaccine: Hepacare

Infection with hepatitis B virus is a public health problem throughout the world. Hepatitis B vaccines are now included in national immunization programmes of infants and/or adolescents in 129 countries. Current single antigen vaccines, that are plasma-derived or produced by recombinant DNA technology are highly effective, but between 5-10% or more of healthy immunocompetent subjects do not mount an antihepatitis B surface antibody protective response and others respond poorly (hyporesponders). The inclusion of pre-S1 and -S2 components of hepatitis B surface antigen in addition to the single antigen (triple antigen) in a novel vaccine, Hepacare, Medeva Pharma Plc, Speke, UK, overcomes nonresponsiveness and hyporesponsiveness in a significant number of individuals. The triple antigen is indicated for vaccination of nonresponders (and hyporesponders) to the current single antigen vaccines and for persons who require rapid protection against hepatitis B infection.     

Immunogenicity of 20 μg of recombinant DNA hepatitis B vaccine in healthy neonates: A comparison of three different vaccination schemes

The immunogenicity of a full dose (20 μg) of recombinant DNA yeast-derived hepatitis B vaccine (Engerix-B) was assessed in healthy neonates in order to compare three candidate vaccination schemes. After randomization 162 newborns of hepatitis B surface antigen (HBsAg) negative mothers entered the study. Neonates received hepatitis B vaccine according to a fourdose vaccination scheme starting either at month 3 (scheme I: months 3,4,5, and 11) or at birth (scheme III: months 0,1,2, and 11). Another group of neonates received hepatitis B vaccine according to a three-dose scheme starting at birth (scheme II: months 0, 1, and 6). Serious adverse reactions were not observed; 2.5% of the vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of vaccination scheme; all infants developed anti-HBs levels ≥10 IU/L, 97% ≥100 IU/L. The immunogenicity of hepatitis B vaccine after primary and booster vaccinations, administered in the four-dose scheme started at birth, was significantly higher (P< 0.05) than in the three-dose scheme started at birth. Hepatitis B vaccination according to the four-dose scheme started at month 3 produced significantly higher (P < 0.05) antibody levels in comparison to the four-dose scheme started directly after birth. This study showed that a fourdose hepatitis B vaccination scheme starting at month 3 resulted in the highest antibody levels of the three schemes investigated and can be recommended for incorporation in the Expanded Programme on Immunization in The Netherlands.     

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.     

Prevention of perinatal transmission of hepatitis B virus (HBV): a comparison of two prophylactic schedules

Perinatal transmission of hepatitis B virus (HBV) from HBsAg carrier mothers who were HBeAg+, antiHBe+, or negative for both HBe markers, was interrupted using either 4 doses of vaccine, or one dose of hepatitis B immunoglobulin (HBIG) at birth, combined with 4 doses of vaccine. In those infants who received HBIG at birth, the antiHBs titre was significantly higher at 1 and 2 months old, but at 6, 9, and 18 months old, there was no significant difference. Among the infants of carrier mothers who did not display HBeAg (i.e., were antiHBe+, or negative for both HBe markers), a transient subclinical infection would have been expected in around 10% had there been no intervention. No evidence of such infection was detected, and no difference in outcome was found between the two treatment groups. Amongst infants born to HBeAg+ carrier mothers, infection occurred in 1 out of 8 who had received HBIG and vaccine, and in 3 of 8 who had received vaccine only. The difference in outcome was not statistically significant, but the numbers analysed were small. The infections which occurred in spite of prophylaxis may be attributable to in utero infection, poor response to vaccine by the infant, or to the mother having a particularly high HBV-DNA level. HBIG given at birth to infants of HBeAg+ carrier mothers may enhance the protection of infants who are destined to be poor responders to vaccine.     

Hepatitis B immunization in high risk neonates born from HBsAg positive mothers: comparison between plasma derived and recombinant DNA vaccine

A half dose recombinant hepatitis B vaccine (HBVax II, MSD, 5 micrograms) was investigated for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers as compared to the half-standard dose regimen of plasma derived hepatitis B vaccine (HBVax, MSD, 10 micrograms). Forty infants born to carrier mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either the recombinant or plasma derived hepatitis B vaccine. The infants were randomly divided into two groups of 20 infants each. The plasma derived vaccine (10 micrograms) was given to group I, while infants in group II received the recombinant vaccine (5 micrograms) at birth, 1 and 6 months of age. There were no statistically significant differences in the efficacy and the seroconversion rate of these two combined prophylaxis regimens. The protective efficacy rate of both kinds of HBV vaccine was found to be 94.6 and 89.2 percent in group I and group II respectively. At twelve months of age, the anti-HBs seroconversion rates were 95.0 percent in group I and 84.2 percent in group II. However, the geometric mean titres in group I (179.55 mIU/ml) was significantly higher than those in group II (42.2 mIU/ml) but the anti-HBs titre was still above protective level (10 mIU/ml) in most of the infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-cost hepatitis B vaccine improves uptake among self-paying health-care students.

Advisory committees recommend hepatitis B (HBV) immunization for professional and student health-care workers. However, the currently licensed vaccines are expensive, and previous surveys have shown that few students (14%) have been immunized in Canada. A low-cost immunization program was offered to health-care students in order to determine whether the effectiveness of HBV immunization could be improved by substantially reducing the vaccine cost to recipients. The immunogenicity, side effects, and 3-dose completion rate of a low-cost Korean HBV vaccine were compared with a similar U.S.-made vaccine. A total of 922 postsecondary students enrolled in 6 health-care disciplines in Ottawa, Canada were surveyed for hepatitis-B immunization status. Nonimmunized students were subsequently offered HBV vaccine at total cost of $15 (Canadian), randomly allocated to receive 3 intramuscular doses of either Korean or U.S.-made plasma-derived HBV vaccine in a double-blind fashion, surveyed about side effects, and tested for hepatitis B surface antibody seroconversion. Only 12% of the 922 surveyed students had been previously immunized when vaccine was obtainable only at high cost. However, 66% of those not immunized participated in the vaccine trial and paid the $15 fee. Hepatitis-B surface antibody seroconversion (greater than or equal to 10 sample ratio units by radioimmunoassay) occurred in 291/311 (93.6%) and 299/310 (96.5%) of recipients of 3 doses of the Korean and U.S. vaccines, respectively (P = 0.10). There were no meaningful differences in vaccine adverse effects, and 92.6% of recipients of either vaccine completed 3 doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

A mathematical model predicting anti-hepatitis B virus surface antigen (HBs) decay after vaccination against hepatitis B

The determination of serum levels of antibodies against hepatitis B virus surface antigen (anti-HBs) after hepatitis B vaccination is currently the only simple test available to predict the decay of protection and to plan the administration of booster doses. A total of 3085 vaccine recipients of plasma-derived and recombinant vaccine have been followed for 10 years to determine the kinetics of anti-HBs production and to construct a mathematical model which could efficiently predict the anti-HBs level decline. The anti-HBs peak level was reached 68 days after the last dose of recombinant vaccine and 138 days after the last dose of plasma-derived vaccines. The age of vaccinees negatively influenced the anti-HBs levels and also the time necessary to reach the anti-HBs peak. A bilogarithmic mathematical model (log10 level, log10 time) of anti-HBs decay has been constructed on a sample of recombinant vaccine recipients and subsequently validated on different samples of recombinant or plasma-derived vaccine recipients. Age, gender, type of vaccine (recombinant or plasma-derived), number of vaccine doses (three or four) did not influence the mathematical model of antibody decay. The program can be downloaded at the site: http:@www2.stat.unibo.it/palareti/vaccine.htm . Introducing an anti-HBs determination obtained after the peak, the program calculates a prediction of individual anti-HBs decline and allows planning of an efficient booster policy.     

Hepatitis B immunization in high risk neonates born from HBsAg and HBeAg positive mothers: comparison of standard and low dose regimens

A reduced dose of plasma derived hepatitis B vaccine (Hevac B) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in high risk neonates born from e-antigen positive HBsAg carrier mothers. Forty newborn infants born of these mothers were given hepatitis B immune globulin (HBIG) 100 IU intramuscularly immediately after birth, combined with either standard or reduced doses of HBV vaccine. The infants were divided into two groups of 20 infants each. The standard dose of HBV vaccine (5 micrograms) was given to group I, while infants in group II received reduced dose (2 micrograms) at birth and at 1, 2 and 12 months of age. There was no statistically significant difference in the efficacy and antibody responses of these two combined prophylaxis regimens. The protective efficacy rate of HBV vaccine was found to be 94.0 and 93.2 percent in group I and group II, respectively. At twelve months of age, the anti-HBs seroconversion rates were 80.0 percent in group I and 86.7 percent in group II, with geometric mean titres of 84.57 mlU/ml and 78.56 mlU/ml, in group I and group II, respectively. One month after a booster at one year of age, anti-HBs could be detected in 86.7 percent of the infants in both groups. The geometric mean titres were 429.04 and 664.81 mlU/ml, in group I and group II, respectively. Anti-PreS2 antibody was detected in high titre as early as 4 months after the first dose of HBV vaccine, with a geometric mean titre of 116.30 mlU/ml and 107.97 mlU/ml, in group I and group II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of the antigenicity and immunogenicity of a new hepatitis B vaccine using a panel of monoclonal antibodies

The successful prevention of infection with hepatitis B virus (HBV) has been achieved by vaccination with purified hepatitis B surface antigen (HBsAg). The ability of a novel synthetic HBV envelope antigen vaccine (Hep B-3, Hepagene ™; Medeva), which contains part of the pre-S1 and the complete pre-S2 regions and the whole of the S region and was produced in a mammalian cell line, to induce antibodies required for a protective immune response is of importance. In this study, the use of a panel of monoclonal antibodies known to bind to epitopes within the common “a” determinant has demonstrated that the epitopes present on this new vaccine are comparable to those found with plasma-derived HBsAg. In addition, the epitope specificity of the antibodies induced by this vaccine was examined and shown to accord well with previous results obtained using both a plasma-derived vaccine and a recombinant vaccine prepared in yeast. J. Med. Virol. 54:1–6, 1998. © 1998 Wiley-Liss, Inc.     

Recombinant Hepatitis B Vaccine

Recombinant hepatitis B vaccine Engerix B((R)) [Hep-B(Eng)] is a noninfectious subunit hepatitis B viral vaccine indicated for the active immunisation of adults, children and infants against hepatitis B virus infection. It contains hepatitis B surface antigen (HBsAg) which is produced by the yeast Saccharomyces cerevisiae by use of recombinant DNA technology. In adults and children seroprotection rates [anti-HBsAg antibody (anti-HBs) titres >/=10 IU/L] were 93 to 100% 1 month after completion of the immunisation schedule with Hep-B(Eng) [0, 1, 6-month schedule]. A more rapid immunological response has been reported with accelerated Hep-B(Eng) immunisation schedules, such as the 0, 1, 2, 12-month schedule. Hep-B(Eng) produces seroprotection rates similar to those achieved with the plasma-derived vaccines and the recombinant hepatitis B vaccine, Recombivax-HB((R)) [Hep-B(Rax)] when administered at recommended doses. In studies in Taiwanese and Thai neonates born to hepatitis B carrier mothers, seroprotection rates were >/=94% 12 months after immunisation with Hep-B(Eng) [+/- hepatitis B immunoglobulin (HBIG)] and protective efficacy was high, with 相似文献   

Accelerated schedule of hepatitis B vaccination in patients with hemophilia

Early development of immunity after hepatitis B vaccination is particularly important for patients such as hemophiliacs, at high risk for acquiring hepatitis B from potentially infectious plasmaderived concentrates. The purpose of this study was to evaluate whether or not protective antibody titers could be achieved quickly and maintained in hemophiliacs by an accelerated vaccination schedule. A yeast-recombinant hepatitis B vaccine (Engerix B, SKF Ritt) was given subcutaneously in the deltoid region and repeated 2 and 6 weeks later to 85 hemophiliacs negative for hepatitis B virus (HBV) markers. After the first 22 patients had been enrolled, a modification of the schedule involving a fourth booster dose 24 weeks after the first dose of vaccine was applied to the next 63 consecutive vaccinees. Fifty-three percent of vaccinees had antibody titers to hepatitis B surface antigen (anti-HBs≥ 10 mlU/ml) by week 6, even though the mean titers of anti-HBs were somewhat lower than those achieved historically in normal individuals. The protection rate had increased to 87% by week 10, one month after the third dose of vaccine, and to 93% by week 24. One year after starting vaccination, the rate for the vaccinees who did not receive the fourth booster dose was 71%, and 96% for those who did receive the fourth dose, with only 2 patients not responding despite the booster dose. It is concluded that even though the accelerated schedule of immunization produced rapidly high rates of protective antibody titers, a booster dose is required to obtain higher titers and provide more persistent immunity.     

Prevention and control of hepatitis B in China

About 170 million Chinese are infected chronically with HBV and 10% suffer from chronic hepatitis. Around half a million Chinese die from hepatitis B caused hepatocellular carcinoma and endstage cirrhosis each year. From 1983 to the present, a controlled clinical trial involving 80,000 children on a universal hepatitis B vaccination programme to prevent chronic hepatitis, hepatocellular carcinoma, and endstage cirrhosis was implemented in Qidong, China. A pilot study demonstrated that the HBsAg rate reached the adult level before the fifth year of age, and neonatal vaccination with either plasma-derived or recombinant hepatitis B vaccines provided a similar 75% protective efficacy against HBV infection. The high rate of follow-up and blood tests coverage of the cohorts provided data to show 75% protection at the tenth to eleventh years of age against serum HBsAg and also against prolonged hepatic dysfunction. The strategy of controlling hepatitis B nationwide was based on the universal immunisation of newborns, beginning in cities and then the rural areas. The large-scale vaccine source was provided by domestic plants through technology transfer, first providing plasma-derived vaccine replaced completely by recombinant DNA vaccine in 1997. An official survey in 1999 using a cluster sampling of 25,878 children from 31 provinces reported an average coverage rate of three dose of hepatitis B vaccination of 70.7%, being higher in urban areas. The Ministry of Public Health of China has planned to integrate hepatitis B vaccination into the nationwide EPI program with Government-provided vaccines starting January 1, 2002.     

Simultaneous administration of hepatitis B and yellow fever vaccines

In most developing countries, hepatitis B prevention is carried out early in life. In these countries, mobile immunization teams have a limited number of sessions to devote to each rural community; simultaneous administration of multiple antigens is thus normal practice. We compared the immune responses of Senegalese children to the separate or simultaneous injections of yellow fever and hepatitis B vaccines. Injections were given at the time of booster injection for hepatitis B vaccine. Yellow fever antibodies were detected in similar proportions in infants immunized with either yellow fever vaccine alone or yellow fever and hepatitis B vaccines simultaneously. However, a lower proportion of high yellow fever antibody levels were observed when the two vaccines were injected simultaneously. No reduction in the anamnestic response of antibodies against the surface antigen of hepatitis B virus (anti-HBs) was observed when yellow fever vaccine was injected at the same time as the booster dose of hepatitis B vaccine. Since no untoward reactions were noted, it is concluded that hepatitis B and yellow fever vaccines can be administered at the same time.     

Immunogenicity of low doses of hepatitis B vaccine in children: a study in 650 New Zealand children

Six hundred and fifty New Zealand children from 2-12 years of age were vaccinated three times with 2 mcg intramuscular (IM) doses of Merck Sharp and Dohme plasma-derived hepatitis B vaccine (H-B-Vax), at 0, 1, and 6 months, and tested 2-3 months later for antibody to hepatitis B surface antigen (anti-HBs) by radioimmunoassay (RIA). Overall, 96.5% of the children seroconverted for anti-HBs by RIA, having levels greater than 2.1 RIA S/N units, with 91.2% having values greater than 10 S/N units. Anti-HBs levels were also determined by enzyme immunoassay (EIA), by which method a significantly better response was demonstrated in 2-4-year-olds than in older children. This study demonstrated that a satisfactory anti-HBs response was obtained using one-fifth of the recommended doses of hepatitis B vaccine.     

乙肝疫苗联合乙肝免疫球蛋白对阻断母婴垂直传播乙型肝炎病毒的临床分析

目的探讨孕妇产前用乙肝免疫球蛋白（HBIG）与乙型肝炎疫苗联合免疫阻断母婴传播的效果。方法将504例HBsAg（＋）孕妇分为A（预防组）,B（对照组）两组。A组：246名HBsAg阳性孕妇孕晚期每月分别注射基因重组型乙肝疫苗10μg、HBIG200IU（200IU/ml）,新生儿出生后采股静脉血,同时在出生后24h内注射HBIG200IU,然后在0、1、6月龄接种基因重组型乙肝疫苗,每次10μg。B组：258例产前未注射HBIG和基因重组型乙肝疫苗的HBsAg阳性孕妇,其所生新生儿在0、1、6（30μg、30μg、30μg）月龄只用基因重组型乙肝疫苗免疫。A、B两组婴儿都分别在0、3、6、9、12、24月龄静脉采血,用酶联免疫吸附试验（ELISA）检测HBV标志物,同时随访。结果A组的宫内感染率为3.25%,B组为4.16%,差异无统计学意义（χ^2=1.43,P〉0.05）。A组没有发生慢性HBV感染的婴儿,而B组中有7例婴儿发生慢性HBV感染,B组婴儿发生慢性HBV的感染率显著高于A组（χ^2=4.41,P〈0.05）。结论产前用HBIG和新生儿HBIG联合免疫可降低慢性HBV感染率,阻断宫内感染的慢性化,提高产程感染的阻断效果。     

Inadequacy of immunoglobulin M hepatitis B core antibody in detecting acute hepatitis B virus infection in infants of HBsAg carrier mothers

To study the usefulness of IgM hepatitis B core antibody (anti-HBc IgM) for detecting hepatitis B virus infections in infants of hepatitis B surface antigen (HBsAg) carrier mothers, serial serum samples from 86 infants of carrier mothers were tested for anti-HBc IgM with a highly specific enzyme immunoassay. Asymptomatic hepatitis B infection occurred frequently in infants under 12 mo of age. Anti-HBc IgM never became positive in 25 infants infected under 9 mo old. It was positive in only 1 of 6 infected at 9 mo and 4 of 13 infected at 12 mo of age. The IgM antibody lasted for less than 6 mo. Although the infection was delayed in 28 infants receiving hepatitis B immune globulin, the poor anti-HBc IgM response did not seem to be due to the immune prophylaxis. Our study clearly indicates the limitation of anti-HBc IgM for detecting acute hepatitis B infection in infants born to HBsAg carrier mothers.