Depression of the immune response to an inactivated hepatitis A vaccine administered concomitantly with immune globulin. Comparison of two lots of immune serum globulin for prophylaxis of infectious hepatitis. Efficacy of different doses of immune serum globulin in the prevention of hepatitis A: a three-year prospective study. [Effect of the content of hepatitis A antibodies in immunoglobulin preparations on the effectiveness of the immunoglobulin prophylaxis of hepatitis A]. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. Pre-exposure prophylaxis with immune serum globulin for prevention of viral hepatitis in army recruits. [Experience with the use of immunoglobulin prophylaxis of hepatitis A in the lithuanian SSR. The prophylactic action of different doses of a commercial immunoglobulin depending on the epidemic situation]. Pre-exposure prophylaxis of viral hepatitis with immune serum globulin in an endemic area. A trial in field units of the Israel Defence Forces. Safety, tolerability, and immunogenicity of an inactivated hepatitis A vaccine: effects of single and booster injections, and comparison to administration of immune globulin.
Inactivated hepatitis A virus (HAV) vaccine is given in a three-dose schedule. When rapid protection is needed, injection of immune globulin (IG) concomitantly with the first dose could provide passive protection until adequate active antibody response has developed. A possible effect of IG on the immune response to the vaccine was studied in healthy volunteers; 28 received vaccine alone, and 34 received the first dose simultaneously with 5 mL of IG. A control group received hepatitis B vaccine, and a fourth group received IG alone. Four weeks after the first vaccine dose, all subjects had detectable ELISA anti-HAV antibodies. Several weeks after each vaccine dose, the geometric mean titer of antibodies was significantly lower in those who received vaccine with IG but higher than in those who received IG alone. Results for neutralizing antibodies yielded a similar trend. If IG is given with HAV vaccine, a further booster vaccine dose may be required to ensure long-lasting immunity. nan Previous studies have shown that the administration of immune serum globulin (ISG) before exposure to hepatitis A virus prevents infection. The precise dose needed and the duration of the protection conferred are unclear, however. In this study, ISG doses of 2 mL and 5 mL were used for preexposure prophylaxis, and their efficacies in reducing the attack rate of hepatitis A among Israel Defence Forces troops serving in field units were compared. The attack rate during the first 4 months of follow-up was low and was similar regardless of the dose administered (0.11/10,000 and 0.15/10,000 for 2 mL and 5 mL, respectively; P = 1.0). In the second and third 4-month intervals after immunization, attack rates were higher (but not significantly so) among soldiers given 2 mL than among those given 5 mL. Twelve months after immunization, the cumulative attack rate for hepatitis A was significantly different for the two groups (2.78/10,000 vs. 1.30/10,000; P < .05). Our data suggest that preexposure immunization with 2 mL of ISG is as effective as that with 5 mL in preventing hepatitis A for 4 months. The advantage of the 5-mL dose is evident 5-12 months after administration. The results of a strictly controlled experiment showed that prevention of hepatitis A by the injection of immunoglobulin with hepatitis A virus (HAV) antibody titer 1:10000 was 3 times as effective as that achieved with immunoglobulin containing HAV antibodies in titer 1:2500. It is recommended to determine the level of specific HAV antibodies in immunoglobulins and to use immunoglobulins with a high level of HAV antibodies for prevention of hepatitis A. Hepatitis A vaccine administered to persons after exposure to the hepatitis A virus has not been compared directly with immune globulin, which is known to be highly effective in preventing hepatitis A when given within 2 weeks after exposure to the virus.
                We randomly assigned household and day-care contacts, 2 to 40 years of age, in Almaty, Kazakhstan, to receive one standard age-appropriate dose of hepatitis A vaccine or immune globulin within 14 days after exposure to patients with hepatitis A. Instances of laboratory-confirmed, symptomatic hepatitis A infection occurring between 15 and 56 days after exposure were then assessed during active follow-up of all susceptible contacts.
                Of 4524 contacts who underwent randomization, 1414 (31%) were susceptible to hepatitis A virus and 1090 were eligible for the per-protocol analysis. Among these contacts, 568 received hepatitis A vaccine and 522 received immune globulin. Most contacts were children (average age, 12 years), and most received prophylaxis during the second week after exposure (average interval after exposure, 10 days). The baseline characteristics of the contacts were similar in the two groups. Symptomatic infection with hepatitis A virus was confirmed in 25 contacts receiving vaccine (4.4%) and in 17 contacts receiving immune globulin (3.3%) (relative risk, 1.35; 95% confidence interval, 0.70 to 2.67).
                Low rates of hepatitis A in both groups indicate that hepatitis A vaccine and immune globulin provided good protection after exposure. Although the study's prespecified criterion for noninferiority was met, the slightly higher rates of hepatitis A among vaccine recipients may indicate a true modest difference in efficacy and might be clinically meaningful in some settings. Vaccine has other advantages, including long-term protection, and it may be a reasonable alternative to immune globulin for postexposure prophylaxis in many situations. (ClinicalTrials.gov number, NCT00139139 [ClinicalTrials.gov].).
                Copyright 2007 Massachusetts Medical Society. A controlled trial with pre-exposure immune serum globulin was undertaken in Israel Defence Forces (IDF) recruits, an indigenous population living in a hyperendemic area for hepatitis A. The objective was to examine whether the prevailing IDF policy of postexposure administration of immune serum globulin prophylaxis should be modified to further reduce the incidence of infectious hepatitis in the IDF. Altogether 23 447 recruits were systematically allocated on their first day of service into an intervention group and a control group. Over the 18-month follow-up period 18 cases of non-B viral hepatitis were identified among the 10 943 vaccinees and 41 among the 12 504 non-immunised group. Protection over six months was about 85%, and over the entire 18 months 50%. Protection was evident until about 40 weeks' follow-up and may have persisted for longer. Rates in the non-immunised were lower than expected, alluding to the possibility of herd immunity. IDF immunisation policy was successfully altered after this trial. nan Field units in the Israel Defence Forces represent a high risk group for type A infectious hepatitis. Very large scale post-exposure prophylaxis with immune serum globulin (ISG) has been successfully employed for the past decade with a reduction in incidence and an elimination of overt epidemic cycles. The use of pre-exposure prophylaxis in an indigenous population in whom approximately 70% have antibody to HAV at age 18 was compared in a field trial with the routine post-exposure method. Units were randomized into an intervention group (A) in which all subjects were to receive ISG (79% were in fact immunized), a second group (B) in which 50% of subjects were to be immunized (36% were actually immunized) and a non-immunized control group (C). During the trial incidence rates in the non-immunized study population dropped well below predicted levels. The incidence rates were zero in group A, 1.31/1000 in group B (0.61/1000 among the immunized and 1.72/1000 among the non-immunized) and 2.49/1000 in group C over the 6-month follow-up. Pre-exposure ISG afforded excellent protection and even at the low rate of incidence was cost-effective. The possibility of herd immunity is discussed. Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerability, and immunogenicity of a single i.m. injection of IG with single and booster doses of an inactivated hepatitis A virus vaccine (iHAV) in adults. A total of 75 healthy volunteers (aged 18-50 years) were evaluated in two separate studies. The first included 15 volunteers who received 25 units iHAV i.m. at 0 and 24 weeks. The second, a randomly controlled study, consisted of three groups receiving 25 units iHAV i.m. at 0, 1, and 6 months, or at 0, 2, and 6 months, or 0.06 ml/kg IG i.m. given once. Anti-HAV seroconversion was measured by radioimmunoassay (RIA). After IG injection, anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12, and 0% by week 20. In contrast, after a single 25-unit dose, RIA seropositivity in iHAV vaccines was 73% by week 2, reaching 100% by week 5, and persisted in all up to week 24, at which time anti-HAV geometric mean titers (GMT) were 2-fold higher than those seen at week 1 after IG. Administration of a booster dose given 1 or 2 months after primary immunization did not significantly improve the quantitative anti-HAV response at 6 months as compared to the effect of the primary dose.(ABSTRACT TRUNCATED AT 250 WORDS)