Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.     

Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers

OBJECTIVE: To assess the presence of antibody to hepatitis B surface antigen (anti-HBs) at postvaccination testing in Minnesota health care workers receiving recombinant hepatitis B vaccines, and to identify risk factors for lacking anti-HBs following hepatitis B vaccination. DESIGN: Retrospective cohort study. SETTING: Ten acute care hospitals in Minnesota. PARTICIPANTS: A total of 595 health care workers who had received hepatitis B vaccine (Recombivax HB or Engerix-B) between June 1987 and December 1991 and who underwent postvaccination testing for anti-HBs within 6 months after receiving the third dose of vaccine. MAIN OUTCOME MEASURE: Presence or absence of anti-HBs following hepatitis B vaccination. RESULTS: Five variables were independently associated with lacking anti-HBs by multivariate analysis: vaccine brand, smoking status, gender, age, and body mass index. Stratifying by vaccine brand demonstrated that age (P = .01), body mass index (P < .01), and smoking status (P < .01) were associated with lacking anti-HBs only for Recombivax HB recipients; and gender (P = .03) was associated with lacking anti-HBs only for Engerix-B recipients. After controlling for smoking status, age, gender, and body mass index, recipients of Recombivax HB were more likely to lack anti-HBs than recipients of Engerix-B (relative risk, 2.3; 95% confidence interval, 1.1 to 4.7; P = .02). CONCLUSIONS: Results indicate that certain populations of health care workers are at increased risk of not responding to hepatitis B vaccination. Further studies evaluating immunogenicity of currently available recombinant hepatitis B vaccines in persons at high risk for primary vaccine failure are needed.     

Antenatal diagnosis of esophageal atresia with tracheoesophageal fistula

We have studied the antibody response to hepatitis B vaccine in 42 hemodialysis patients; 8 of them were diagnosed as having HCV infection before vaccination. Hemodialysis patients received four doses of recombinant HB vaccine (Engerix-B, SKB, 40 micrograms per dose). Seroconversion occurred in 71.4% of all hemodialysis patients; in 79.4% of HCV-negative and in 37.5% of HCV-positive patients. Effective immunity (anti-HBs titer higher than 100 m IU/ml) was observed in 12.5% of HCV positive and in 35.3% of HCV-negative patients. We conclude that HCV infection may modify or postpone the response to hepatitis B vaccine.     

Evolutional neurologic evaluation of seven year-old children born prematurely

Personnel (1856 subjects) belonging to local health units (medical and paramedical staff) that have been vaccinated since 1984 against hepatitis B virus (HBV) with HBsAg plasma purified preparations (Hevac-B and H-B-Vax) or recombinant DNA preparation (Engerix-B) were followed in plasma anti-HBs antibody levels. At the end of the protocols, different seroconversion percentages and different anti-HBs levels were reached: the best results were obtained with Engerix-B. Sex and principally age influenced the antibody production: women generally reached highest protective antibody levels and the 21-30 year group was more responsive than other groups. The injection of a supplementary 4th or 5th dose in low or non-responders could restore the specific immunity in the majority of the subjects and increase the anti-HBs level. The time course after the immunization of antibody levels depended on the level reached at the end of vaccination schedule. These data suggest that different antibody level monitorings of vaccinated subjects, planned on the basis of the antibody level reached at the end of vaccination, could prevent a loss of protection against the HBV infection.     

Long-term persistence of anti-HBs after vaccination with a recombinant DNA yeast-derived hepatitis B vaccine: 8-year results

The aim of this study was to evaluate the persistence of antibodies 7 years after hepatitis B booster administration in healthy adult volunteers who were vaccinated in 1986. In October 1986, 188 seronegative, healthy adult volunteers (117 men and 71 women) were vaccinated with a 20 micrograms dose recombinant DNA yeast-derived hepatitis B vaccine. Mean age of the study group was 23.3 years (+/- 0.28). Immunisation was carried out according to a 0-1-2 month vaccination schedule, with a booster dose at 12 months. Of the 159 subjects who received the full vaccination course, 63 (40%) had a blood sample taken 8 years after the first vaccination. Of these 63 subjects, five were excluded from the analysis due to an irregular vaccination schedule and four subjects did not complete the accompanying questionnaire on possible booster administration. So, 54 subjects remained available for further analysis. Fourteen individuals had received an additional booster of hepatitis B vaccine sometime between 1989 and 1994. The geometric mean titre (GMT) at month 13 for these 14 individuals was 1494 mIU ml-1, compared with 3103 mIU ml-1 for those who did not receive an interim booster. Forty subjects, who received no additional booster dose besides that of month 12, met the inclusion criteria of the follow-up study. Of these, all subjects except one were seropositive for anti-HBs at month 96 (GMT: 215.9 mIU ml-1). All subjects were still anti-HBc negative at that time. Distribution of individual antibody titres revealed that overall 92.5% of subjects retained protective antibody levels (> or = 10 mIU ml-1); 72.5% of vaccinees retained high levels of anti-HBs (> or = 100 mIU ml-1) as compared to 99.2 and 97.0% at month 13, respectively. A positive correlation was found between the subjects' titres at month 13 and month 96. A 0-1-2 dose vaccination course with a booster dose administered at month 12, induces a protective immune response which lasts at least until 7 years after the full vaccination course of the subjects. A positive correlation was found between the anti-HBs antibody titres at month 13 and month 96.     

Access to a three-dimensional measure of vertebral axial rotation

BACKGROUND: A combined diphtheria-tetanus-whole cell pertussis-hepatitis B (DTPwHB) vaccine might facilitate the achievement of universal vaccination of infants against hepatitis B. METHODS: A double blind, randomized, two-armed, single center study was undertaken to evaluate the immunogenicity and reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of hepatitis B component (10 microg and 5 microg). The combined vaccine was tested in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers after priming with one dose of hepatitis B vaccine (10 microg) at birth. Antibodies to each antigenic component were measured from blood samples collected immediately after birth, pre- and postvaccination blood samples. RESULTS: The reactogenicity profiles were similar in the two groups. No serious adverse events were reported. One month after completion of the four-dose vaccination schedule, all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19). One month after three doses all subjects in both groups had protective antidiphtheria titers and antitetanus titers. The vaccine response rate to the Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in Group 2 (P = 0.86). CONCLUSION: Both combined tetravalent vaccines are safe and immunogenic when administered to infants born to a hepatitis B surface antigen-negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth. This combined tetravalent DTPwHB vaccine may play an important role to promote integration of HB vaccine into the Expanded Program of Immunization in hepatitis B-endemic areas.     

Occlusion of the femoral artery induced fos-like immunoreactive neurons in the lateral habenular nucleus projecting to the midbrain periaqueductal gray in the rat

BACKGROUND: Inactivated hepatitis A vaccines are licensed with a vaccination schedule based on two injections of vaccine given at least 6 months apart. METHODS: Two vaccination schedules for the inactivated hepatitis A vaccine, AvaximTM (Pasteur Mérieux Connaught, Lyon, France), were compared in a monocentric, randomized, open trial. Two doses of the vaccine were given at intervals of either 6 months (0-6 month group) or 12 months (0-12 month group) to 96 adult volunteers. Anti-hepatitis A virus (HAV) antibody titers were determined in a blind fashion using the modified RIA (mRIA) HAVABtrade mark assay. After excluding subjects with positive preimmunization anti-HAV titers and those with protocol deviations, both groups were still comparable by sex ratio and mean age. RESULTS: Four weeks (28 6 4 days) after the first dose, the seroconversion (SC) rate of initially HAV-seronegative subjects (antibody titer < 20 mIU/mL) was 100% in the 0-6 month group and 96. 9% in the 0-12 month group, with corresponding geometric mean titer (GMT) values (95% CI) of 369 mIU/mL (274-497 mIU/mL) and 445 mIU/mL (292-679 mIU/mL), respectively. After 6 months, SC was obtained in all subjects, and the corresponding GMT values were 349 mIU/mL and 359 mIU/mL in the 0-6 month group and the 0-12 month group, respectively. Four weeks after the booster dose given at 6 months, a 14.5-fold rise in GMT was observed. In the 0-12 month group, anti-HAV GMT values decreased by only 20% from 6 months to 12 months with a pre-booster GMT value of 286 mIU/mL at the 12-month evaluation. Four weeks after the booster given at 12 months, a 22. 5-fold rise in GMT was observed. Statistical analysis showed that the two vaccination schedules were comparable in their ability to boost antibody titers. Unsolicited reactions to vaccination were not different to those reported during earlier trials. Less than 12% of the vaccinees reported reactions after the first dose (11/93), or after the booster dose (11/92). CONCLUSIONS: This trial demonstrated antibody persistence is excellent for at least 12 months after one dose of this vaccine, and that a booster may be given at any time between 6 and 12 months after primary immunization.     

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.     

Hepatitis B vaccine containing surface antigen and selected preS1 and preS2 sequences. 1. Safety and immunogenicity in young, healthy adults

The safety and immunogenicity of a yeast-derived recombinant hepatitis B virus (HBV) vaccine containing surface antigen (S) and selected preS1 and preS2 sequences (S-L*) were compared with those of a vaccine prepared with S alone (Engerix-B). S-L* consisted of composite particles containing S and L* at a ratio of 70/30. L* encompassed amino acid residues 12-52 of preS1 residues 133-145 of preS2, and the entire S domain. A total of 100 healthy, HBV-seronegative, young adults were randomized to receive 20 micrograms/dose of either S-L* or Engerix-B under double-blind conditions according to a 0-, 1-, 2-, 12-month schedule. In vivo humoral and in vitro lymphoproliferative responses to S and preS regions were monitored. Addition of the selected preS sequences to S did not enhance the in vivo humoral anti-HBs response but improved the in vitro stimulating capacity of the antigen (L*) in S-L* primed subjects.     

Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age

This double-blind, randomised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine (DTPa-HBV) co-administered with three lots of Haemophilus influenzae type b conjugate (Hib) vaccine in one injection, as a primary vaccination course in healthy infants at 2, 4 and 6 months of age. 269 infants (8-11 weeks of age) were randomly allocated to three groups to receive DTPa-HBV/Hib vaccines, concomitantly with oral polio vaccine. Blood samples for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects. Local and general symptoms were recorded by parents on diary cards. All vaccinees had post-vaccination protective anti-D and anti-T (> or = 0.1 IU ml-1) antibodies, and 98% had protective anti-HBs antibody titres (> or = 10 mIU ml-1). There were no statistically significant differences between groups in post-vaccination anti-D, anti-T, anti-HBs antibody geometric mean titres (GMT), these being 3.49 IU ml-1, 5.92 IU ml-1 and 1109 mIU ml-1, respectively. All subjects responded to three pertussis components, i.e. pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Although statistically significant differences in GMTs of anti-PT, anti-FHA and anti-PRN were found between groups, these were not believed to be of any clinical relevance as the minimum GMTs were 60, 193 and 230 EL.U ml-1 for anti-PT, anti-FHA and anti-PRN, respectively. There were no statistically significant differences in anti-PRP antibody GMT (4.05 micrograms ml-1) between groups, 100% and 85% of subjects having titres > or = 0.15 and 1.0 microgram ml-1, respectively. No symptoms were reported for one third of the subjects. Fever (> 38 degrees C) was reported after 16% of doses, with < 1% having > 39.5 degrees C. Almost all local and general symptoms were mild or moderate, and lasted less than 48 h. No subject dropped out due to a severe adverse reaction. The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe, well-tolerated and immunogenic for all vaccine components.     

Fate of microinjected sperm components in the mouse oocyte and embryo

Combining HB vaccine with routine paediatric vaccines has been recognized as the best means of universal vaccination against hepatitis B. Our objective was to evaluate the long-term antibody persistence of such a combined vaccine in an area of high hepatitis B endemicity. We have shown that a DTPw-HB vaccine was safe and immunogenic when given as a booster dose at 18 months of age. One month after the booster dose of DTPw-HB vaccine, at least 97.8% of subjects had seroprotective anti-HBsAg levels, and 1 year later at least 93.9% of these subjects remained seroprotected against HBsAg. Immune responses to the DTPw components were similar or greater than those of the commercial DTPw vaccine given to the control group. This DTPw-HB vaccine, which showed good long-term anti-HBsAg antibody persistence, could advantageously replace separate DTPw and HB vaccines in areas of high hepatitis B endemicity in terms of clinical, economic and strategic benefits.     

Juvenile offenders and hepatitis B: risk, vaccine uptake and vaccination status

OBJECTIVE: To determine the hepatitis B vaccination status of juvenile offenders in a custodial setting, their perceived risk of hepatitis B infection, and factors influencing vaccine uptake. DESIGN: 130 males aged 14-17 years resident at the Melbourne Juvenile Justice Centre for at least one week between mid-January and mid-December 1996 were invited to participate; 90 (69%) completed a doctor-administered questionnaire, and blood for serological testing was obtained from 83 of these participants. MAIN OUTCOME MEASURES: Whether hepatitis B vaccine had been offered; whether hepatitis B vaccine had been given; the presence of antibodies to hepatitis B and C; risk factors and self-perceived risk of hepatitis B. RESULTS: About a quarter of participants (22/83) had protective levels of antibody to hepatitis B surface antigen (anti-HBs). Forty (44%) participants reported having been offered hepatitis B vaccine; they were more likely to be vaccinated and have protective levels of anti-HBs. Perceived risk for bloodborne virus infection was low, although two-thirds of participants were at high risk of hepatitis B infection. On serological testing, 6.4% (5/78) were positive for antibody to hepatitis B core antigen (anti-HBc), and a further 2.6% (2) had equivocal antibody levels. Of the 71 who were negative for anti-HBc, 51 (71.8%) were negative for anti-HBs. CONCLUSIONS: The targeted hepatitis B vaccination program has not adequately protected this group at high lifetime risk of hepatitis B. Failure to deliver vaccine may reflect lack of contact with healthcare services, oversight in offering vaccine and reluctance of youth to participate in preventive healthcare measures, often through not seeing themselves to be at risk. Universal approaches to vaccination may be more successful in vaccinating this group.     

Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens

A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.     

Hepatitis B component does not interfere with the immune response to diphtheria, tetanus and whole-cell Bordetella pertussis components of a quadrivalent (DTPw-HB) vaccine: a controlled trial in healthy infants

The aim of this single-blind, parallel trial was to assess whether the hepatitis B (HB) component of a DTPw-HB vaccine interferes with the immune response to the other three components when administered at 3, 5 and 7 months of age. One hundred and six infants were randomized to receive three doses of DTPw or DTPw-HB vaccines. Seroprotection (or seroresponse) rates and geometric mean titers (GMT) of antibodies were assessed 3-6 weeks after the third dose. Anti-diphtheria, anti-tetanus and anti-Bordetella pertussis antibodies were measured by ELISA and anti-HBs by radioimmunoassay. Local and general signs and symptoms were recorded for a 4-day follow-up period after each vaccination. After the full vaccination course all subjects in both groups had seroprotective titers (> or = 0.1 IU ml-1) against diphtheria and tetanus and seroresponded (titers > or = 15 EL.U ml-1) to B. pertussis, and there was no significant difference between groups in relation to GMT. All subjects vaccinated with DTPw-HB had seroprotective levels (> or = 10 mIU ml-1) of anti-HBs antibodies after the third dose (GMT of 2318 mIU ml-1). Overall there were no significant differences between groups in relation to the incidence of local and general symptoms. These results show that the HB component did not interfere with the immune response to the other three components of the vaccine.     

Suboptimal response following intradermal hepatitis B vaccine in infants

Two hundred and twenty-five infants were randomly assigned to receive 2 micrograms of plasma-derived hepatitis B vaccine (Heptavax) intradermally (ID-2), 10 micrograms intramuscularly (IM-10), or 2 micrograms intramuscularly (IM-2) in the deltoid region at birth, 2 and 4 months. At 6 months, ID-2 infants were less likely to have developed > or = 10 mIU ml-1 of antibody to hepatitis B surface antigen (anti-HBs) than IM-10 infants (91 versus 100%; p = 0.02) and had a lower geometric mean concentration of anti-HBs (312 mIU ml-1 versus 2248 mIU ml-1; p < 0.01). At 6 months IM-10 infants had significantly lower mean weights and lengths than infants receiving 2 micrograms doses of vaccine. Intramuscular administration of 2 micrograms and 10 micrograms doses of Heptavax in the deltoid of young infants was well tolerated and effective; however, intradermal administration of Heptavax provided no immunological benefit over intramuscular administration and resulted in significantly higher rates of induration and persistent hyperpigmentation. Intramuscular immunization at birth, 2 and 4 months is an acceptable, effective alternative schedule for immunizing infants.     

An epidemic of varicella in rural southern India

Hepatitis B remains a significant risk to patients receiving chronic hemodialysis. Hepatitis B vaccines are effective in providing protection against this infection. However, the minimum antibody level necessary to guarantee an efficacious protection is not clear. Little is known about the effect of this vaccine in persons treated with erythropoietin (EPO) and in patients with hepatitis C virus (HCV) infection. We have studied 36 chronic hemodialysis patients; 17 of them receiving EPO and 9 were diagnosed as having HCV infection. Effective immunity (antibody titer higher than 100 mIU/ml) was observed in 61.1% of the participants and was not influenced by EPO administration, but the effective immunization rate was lower in HCV infected patients (33.3% vs. 70.3%, p < 0.05). These results suggest the possibility that HCV infection may modify the effectiveness of hepatitis B vaccine.     

Ogura and Powers: "Functional restitution of traumatic stenosis of the larynx and pharynx." (Laryngoscope 1964;74: 1081-1110)

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6-12 weeks of age) received three doses of DTPw-HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU.ml-1], anti-diphtheria and anti-tetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.     

Prevention of hepatitis A virus infection

Hepatitis A virus infection is major cause of acute hepatitis in the United States, accounting for approximately 75,000 cases of clinical illness each year. These infections occur among persons in every age group and are associated with a variety of exposures related to fecal-oral transmission. Recently, the U.S. Food and Drug Administration approved licensure of two inactivated hepatitis A vaccines. Both vaccines are highly immunogenic and have been licensed in pediatric and adult formulations. The prevention of hepatitis A virus infection is directly related to many aspects of family practice, and family physicians may see patients in a variety of settings that warrant administration of hepatitis A vaccine. Groups for whom vaccination is currently recommended include international travelers, children in communities with high rates of hepatitis A virus infection, men who have sex with men, Illicit drug users, patients with chronic liver disease and persons with clotting factor disorders.     

Hepatitis A vaccination

The safety and immunogenicity of an inactivated hepatitis A virus vaccine were assessed in 101 healthy adults. Seronegative persons with normal serum aminotransferase levels were grouped according to age: Group 1 (n = 24) and group 3 (n = 22) were between 18 and 40 years of age, and group 2 (n = 25) and group 4 (n = 30) were older than 40 years. Groups 1 and 2 received vaccine on a 0-, 1-, and 2-month schedule (schedule A), and groups 3 and 4 received the vaccine on a 0-, 1-, and 12-month schedule (schedule B). Of the 101 vaccinated subjects, 98 (97%) seroconverted with antibody titers to hepatitis A virus of > or = 20 IU per liter after the first dose, and all subjects seroconverted after the second dose. The geometric mean titers a month after the third vaccine dose were significantly greater (P < .03) on both schedules for younger subjects (schedule A, 1,743 IU per liter, and schedule B, 7,882 IU per liter) than for older subjects (schedule A, 826 IU per liter, and schedule B, 4,279 IU per liter). Also, the differences in geometric mean titers a month after the third dose were significantly greater (P < .001) for subjects in both age groups on schedule B (group 3, 7,882 IU per liter, and group 4, 4,279 IU per liter) than for those on schedule A (group 1, 1,743 IU per liter, and group 2, 826 IU per liter). The hepatitis A virus was well tolerated, with mild discomfort at the injection site being the main side effect. This vaccine is both safe and highly immunogenic.     

Long-term follow-up of hepatitis A vaccination in children

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.