Dose Of Inactivated Hepatitis Research Articles

Safety of concomitant administration of inactivated hepatitis A vaccine with other vaccines in children under 16years old in post-marketing surveillance.

Concomitant administration refers to the receipt of two or more vaccines during a single healthcare encounter, which is an efficient way to increase vaccination coverage in children. However, the post-marketing safety studies of concomitant administration are scarce. Inactivated hepatitis A vaccine (Healive®) has been used widely in China and other countries for more than a decade. We aimed to explore the safety of Healive® co-administered with other vaccines compared to Healive® alone in children under 16years old. We retrieved Adverse Events Following Immunization (AEFI) cases and vaccination doses of Healive® during 2020-2021 in Shanghai, China. The AEFI cases were divided into concomitant administration group and Healive® alone group. We used administrative data on vaccine doses as denominators to calculate and compare crude reporting rates between groups. We also compared baseline gender and age distribution, clinical diagnoses, and time interval from vaccination to onset of symptoms between groups. A total 319,247 doses of inactivated hepatitis A vaccine (Healive®) were used and 1,020 AEFI cases (319.50 per million doses) associated with Healive® were reported during 2020-2021 in Shanghai. There were 259,346 doses concomitantly administered with other vaccines and 830 AEFI cases (320.04 per million doses) were reported. There were 59,901 doses of Healive® that vaccinated alone, with 190 AEFI cases (317.19 per million doses). There was only one case with serious AEFI in concomitant administration group, with a rate of 0.39 per million doses. Reported rates of AEFI cases were similar between groups in general (p>0.05). Concomitant administration of inactivated hepatitis A vaccine (Healive®) with other vaccines has a similar safe profile as Healive® alone.

Seven-year follow-up of the immune response after one or 2 doses of inactivated hepatitis A vaccine given at 1 year of age in the Mendoza Province of Argentina

ABSTRACTThis monocenter, descriptive, prospective, non-interventional study evaluated the long-term immune responses following routine vaccination with one or 2 doses of a licensed inactivated hepatitis A (HA) vaccine (Avaxim® 80U Pediatric) at age 11–23 months in a cohort of children from Mendoza, Argentina. Antibodies to hepatitis A virus (anti-HAV) were quantified annually up to Y5, and at Y7. Children whose titer decreased to below the seroprotection threshold (defined as an anti-HAV antibody concentration of ≥ 10 mIU/mL in a microparticle enzyme immunoassay up to Y5, or ≥ 3 mIU/mL in an electrochemiluminescence immunoassay at Y7) received a routine booster dose of the same HA vaccine. This report summarizes the data at 7 year after the first vaccination. Of 546 participants initially included, 264 participants remained at Y7 and provided blood samples. Of these, 204 having received one HA primary dose as a toddler were still seroprotected at Y7; titers for a further 7 also having received one HA dose as a toddler fell to below the seroprotection threshold and they therefore received a booster; all 53 having received 2 HA doses as a toddler and still present at Y7 remained seroprotected at Y7. One or 2 primary doses of this HA vaccine in toddlers result in very good persistence of anti-HAV up to 7 year post-first vaccination.

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Immunogenicity and estimation of antibody persistence following vaccination with an inactivated virosomal hepatitis A vaccine in adults: A 20-year follow-up study

PurposeThis was a 20-year follow-up study to assess long-term persistence of protective antibody levels against the hepatitis A virus (HAV) in healthy participants vaccinated with 2 doses of inactivated hepatitis A vaccine (Epaxal®) between 1992 and 1995. MethodsBlood samples for anti-HAV antibody concentrations were obtained during a follow-up visit 20years after vaccination and were analyzed in parallel with samples still available from previous visits using AxSYM® HAVAB 2.0 assay. ResultsMean (SD) age of the participants was 44.71 (3.905) years at year 20 follow-up (N=95). Participants completing 0/12-month Epaxal® immunization regimen (N=94) had seroprotection rate of 100% (95% CI: 96.2, 100.0) with ⩾10mIU/mL seropositivity cut-off and 98.9% (95% CI: 94.2, 100.0) with ⩾20mIU/mL cut-off. With ⩾10mIU/mL cut-off, the estimated median duration of protection was 77.3years (95% CI: 71.8, 83.5) with 95% of the vaccinated participants predicted to be protected for at least 41.5years. At ⩾20mIU/mL cut-off, the estimated median duration of protection was 64.8years (95% CI: 60.1, 68.4) with 95% of the vaccinated participants predicted to be protected for at least 33years. Anti-HAV antibody geometric mean concentrations were higher in women (277.9; 95% CI: 217.7, 354.7) than in men (167.7; 95% CI: 125.2, 224.6). ConclusionThe data from this 20-year follow-up study confirm previous observations that two doses of Epaxal® provide protection against hepatitis A infection for at least 30years in over 95% of healthy participants.

Long-term Durability of Responses to 2 or 3 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Adults on Antiretroviral Therapy.

Previous studies have shown that the durability of serological response is impaired in successfully vaccinated human immunodeficiency virus-1 (HIV-1) positive subjects after receiving 2 doses of inactivated hepatitis A virus (HAV) vaccine. We evaluated whether 3 doses compared with 2 doses of HAV vaccine could improve the long-term seroprotection for this susceptible group. Antibody persistence among HIV-positive men who have sex with men aged 18-40 years who had received 2 or 3 doses of HAV vaccine according to a 0-6- or a 0-1-6-month schedule was evaluated biannually for 5 consecutive years in this prospective, nonrandomized cohort study. At the end of 5 years, seroprotection persisted in 79% (146/185) versus 76% (85/110) and 94% (146/155) versus 88% (84/95) of the 3- versus 2-dose primary responders by intention-to-treat and per-protocol analyses, respectively (P > .05). Throughout the 5 years, the geometric mean concentrations of anti-HAV immunoglobulin G (IgG) were significantly higher for the 3-dose than the 2-dose group. In the multivariable analysis, a 3-dose regimen compared with a 2-dose regimen (odds ratio = 3.36; 95% confidence interval = 1.14-9.93) was independently associated with sustained seroprotection. Three doses versus 2 doses of HAV vaccine improve the durability of immune responses in terms of higher concentrations of specific IgG, which take longer to decay to subthreshold levels.

Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

ABSTRACTObjective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values < 0.001) and 24 months (p-values < 0.0001). Average GMCs for the H2, Healive®, Havrix®, and control groups, in mIU/ml, were 29.7, 81.0, 36.4, and 2.9, respectively at 12 months, and 30.9, 112.2, 44.3, and 2.9, respectively, at 24 months. GMCs were greater for Healive® than for H2 and Havrix® at 12 months (p-values < 0.0001 and < 0.001, respectively) and 24 months (p-values < 0.001). No statistically significant differences in seropositivity or GMC were found within groups between 12 and 24 months. Conclusion: Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine.

Comparison of Immunogenicity Between Inactivated and Live Attenuated Hepatitis A Vaccines Among Young Adults: A 3-Year Follow-up Study.

A randomized clinical trial of hepatitis A vaccines (1 or 2 doses of inactivated vaccine [Healive] or 1 dose of live attenuated vaccine [Biovac]) was conducted among adults to evaluate seroprotection rates and geometric mean concentrations of antibody against hepatitis A virus for 36 months. High rates of seroprotection persisted for at least 36 months among adults who received 1 or 2 doses of inactivated hepatitis A vaccine but not among adults who received 1 dose of live attenuated hepatitis A vaccine. The long-term serial monitoring of immunogenicity induced by 1 dose of inactivated hepatitis A vaccine is needed to determine an effective alternative to a 2-dose schedule. NCT01865968.

Persistence of immunity from 1 year of age after one or two doses of hepatitis A vaccine given to children in Argentina.

BackgroundThis study was done to determine the immunogenicity of a single dose of hepatitis A vaccine in children, providing needed clinical data on the flexibility of booster administration.MethodsParticipants had received one dose of inactivated hepatitis A vaccine (Avaxim™ 80 U Pediatric) at 12–23 months of age or two doses of the same vaccine at 12 and 18 months of age prior to enrolment. Anti-hepatitis A antibody concentrations were measured at the first, second, and third year after vaccination. Suspected cases of hepatitis A in participant families were assessed and family socioeconomic data were collected.ResultsA series of 546 participants were enrolled. Of 467 (85.5%) participants completing 3 years of follow-up, 365 had received a single vaccine dose and 94 had received two vaccine doses. Seropositivity (anti-HAV ≥ 10 mIU/mL) at 3 years was 99.7% after one dose and 100% after two doses. At one year, geometric mean concentrations were higher after two doses (1433.9 mIU/mL, 95% confidence interval [CI] 1108–1855) than one (209.7 mIU/mL, 95% CI 190.6–230.6). Geometric mean concentrations decreased in both groups during the study, but remained well above 10 mIU/mL through the third year. The geometric mean of 3-year to one-year anti-hepatitis A concentration ratios was 0.74 (95% CI 0.70–0.79) following one dose and 0.57 (95% CI 0.47–0.70) following two doses. The greatest decrease in geometric mean concentrations occurred during the third year, ie, 21.2% in the one-dose group and 40.8% in the two-dose group. Six participants became seronegative during follow-up and responded strongly to a booster dose. Anti-hepatitis A concentrations increased in 135 children (34.9%) in the second year and 50 (13.7%) in the third year; none lived in a family with a case of hepatitis A. Three confirmed cases of hepatitis A occurred in family members. Participants belonged to a middle-income, urban/suburban population with good sanitation facilities and water supplies.ConclusionA single dose of hepatitis A vaccine at 12–23 months of age resulted in hepatitis A seropositivity in all but one vaccinee after 3 years. Increased anti-hepatitis A serum concentrations suggested exposure to wild-type hepatitis A virus in this middle-class socioeconomic environment. Continuing surveillance is required to confirm the effectiveness of a single-dose hepatitis A vaccination; however, the results of the first three years are encouraging.

LONG-TERM IMMUNITY AFTER TWO DOSES OF INACTIVATED HEPATITIS A VACCINE, IN ARGENTINEAN CHILDREN

We examined long-term anti-hepatitis A virus antibody persistence in Argentinean children 10 years after the initial study in which they received 2 doses of inactivated hepatitis A vaccine (Avaxim 80U). Of the 111 children, 48 from the initial trial were enrolled. Of 48, 47 (97.9%) participants had serum anti-hepatitis A virus antibody titers > or =20 mIU/mL, with the geometric mean concentration of 390.91 (+/-370.14) mIU/mL; (95% confidence interval, 282.2-499.5 mIU/mL), range, 36 to 1860.

Immunological priming of one dose of inactivated hepatitis A vaccine given during the first year of life in presence of maternal antibodies

Background: In hepatitis A virus (HAV)-seronegative infants, inactivated hepatitis A vaccines are highly immunogenic. On the contrary, in infants who are HAV-seropositive before vaccination, the interfering effect of passively-transferred maternal anti-HAV antibodies leads to lower post-primary immunization anti-HAV levels, as compared to those achieved by seronegative infants. One possible way to overcome this drawback is to delay hepatitis A vaccination later during the first year of life. The objective of the study was to document the immunogenicity of an inactivated hepatitis A vaccine in 6 months old HAV-seropositive infants, given as two dose regimen consisting of a single primary immunization at 6 months of age, followed by a booster dose 6 months later.Methods: The immunogenicity of one hepatitis A vaccine (Avaxim™ pediatric, Aventis Pasteur) was documented in 108 6 months old, HAV-seropositive infants randomly assigned to receive one priming dose of hepatitis A vaccine either concomitantly with (Group 2) or 2 weeks after the third dose of routine diphteria-tetanus-whole cell pertussis reconstituting lyophilized tetanus conjugated Haemophilus influenzae type b (DTwcP//PRP∼T) vaccine and oral poliomyelitis vaccine (OPV) (Group 1). A booster dose was given 6 months later, concomitantly with MMR vaccine.Results: The 91 infants who were HAV-seropositive (ELISA titer >20mIU/ml) at the moment of primo vaccination remained seropositive 1 month later. Geometric mean titers (GMT) decreased from 292 and 278mIU/ml 1 month after the first dose, to 77.6 and 76.0mIU/ml 6 months after, in Groups 1 and 2, respectively. Post-booster titers increased markedly in both groups, with GMTs of 1731 and 1866mIU/ml and geometric mean post/pre-immunization titer ratios of 22.3 and 24.6, respectively.Conclusions: These results suggest that immunological priming induced by a single dose of Avaxim™ pediatric administered to 6 or 6.5 months old, HAV-seropositive infants is present and should not preclude the use of this vaccine in such populations.

Cost Effectiveness of Vaccinating Food Service Workers against Hepatitis A Infection

Foodborne transmission is an important means of hepatitis A infection that may be reduced through vaccination of food service workers (FSWs). Several states are considering actions to encourage or mandate FSW vaccination, but the cost effectiveness of such policies has not been assessed. We estimated the clinical and economic consequences of vaccinating FSWs from the 10 states with the highest reported rates of hepatitis A. A decision analytic model was used to predict the effects of vaccinating FSWs at age 20 years. It was assumed all FSWs would receive one dose of inactivated hepatitis A vaccine, and 50% would receive the second recommended dose. Parameter estimates were obtained from published reports and Centers for Disease Control and Prevention databases. The primary endpoint was cost per year of life saved (YOLS). Secondary endpoints were symptomatic infections, days of illness, deaths, and costs of hepatitis A treatment, public health intervention, and work loss. Each endpoint was considered separately for FSWs and patrons. We estimate vaccination of 100,000 FSWs would cost $8.1 million but reduce the costs of hepatitis A treatment, public health intervention, and work loss by $3.0 million, $2.3 million, and $3.1 million, respectively. Vaccination would prevent approximately 2,500 symptomatic infections, 93,000 days of illness, and 8 deaths. A vaccination policy would reduce societal costs while costing the health system $13,969 per YOLS, a ratio that exceeds generally accepted standards of cost effectiveness.

Immunoprecipitation and virus neutralization assays demonstrate qualitative differences between protective antibody responses to inactivated hepatitis A vaccine and passive immunization with immune globulin.

Antibodies to hepatitis A virus (anti-HAV) were measured in children from two separate vaccine trials (n = 70) 4 weeks after a dose of inactivated hepatitis A vaccine (VAQTA). The geometric mean titers (GMTs) of anti-HAV were 49.3 and 45.2 mIU/mL by immunoassay, while reciprocal GMTs of neutralizing anti-HAV were 6.5 and 15.0 by an 80% radioimmunofocus inhibition test (RIFIT) and 55.6 and 92.0 by antigen reduction assay (HAVARNA). The GMT of antibody detected by radioimmunoprecipitation (RIPA) was > or =401. These data establish serologic correlates of protection against disease and show that RIPA is most sensitive for detection of early vaccine-induced antibody. Sera collected from adults (n = 20) 7 days after administration of immune globulin contained similar antibody levels by immunoassay (45.1 mIU/mL) and slightly higher GMTs of neutralizing antibody (27.5 by RIFIT and 146 by HAVARNA) but negligible precipitating antibody (GMT, 5.6). These results are best explained by differences in the affinity of antibodies for virus following active versus passive immunization.

Preventing Hepatitis A Infections in Travelers to Endemic Areas

In 1995, 24 million travelers from the United States are anticipated to visit developing countries where hepatitis A is endemic. Passive immunization with immune globulin, before exposure or within two weeks following exposure to the hepatitis A virus, protects against clinical disease in < 70-90% of immunized individuals. The duration of protection, measured in months, is relatively short. Active immunization with a single dose of inactivated hepatitis A virus vaccine appears to provide greater protective efficacy and, based on the persistence of vaccine-induced protective antibodies, should provide protection for years. Booster doses given between six and 12 months are likely to provide immunity that may persist for at least a decade. The inactivated hepatitis A vaccine approved for use in the United States has been clinically well-tolerated; mild transient soreness at the injection site is the most frequently reported adverse reaction. Immunization with inactivated hepatitis A vaccine is a safe and effective method for travelers to endemic areas to protect themselves against this infection.

The immune response to different doses of inactivated hepatitis A vaccine

The immunogenicity and reactogenicity of different doses of hepatitis A vaccine was studied in healthy adult volunteers. Vaccinees (105) were immunized with 6.25, 12.5 or 25 ng of HAV antigen, each dose administered at 0, 1 and 6 months (groups B, C and D); one group (group A) obtained three 6.25 ng doses at 0, 1 and 2 months. After one single dose high seroconversion rates ranging between 63 and 85% were observed in all four groups. All participants had seroconverted after the third dose, irrespective of the antigen content per dose and the vaccination schedule. Geometric mean titers after three doses were 439 IU/l (group A, month 3) and 1492, 963 and 2772 IU/l in groups B, C and D at month 7. One year after the first injection all vaccinees tested still showed antibody levels well above 10 IU/l. The vaccine was very well tolerated. Minor localized symptoms were observed mainly such as slight pain at the injection site. These symptoms were not dose related; no serious side effects occurred.

Prevention of viral hepatitis B in early infancy--hepatitis B vaccine (HBVac)

Three doses of inactivated hepatitis B vaccine were given to 33 healthy children aged less than 5 years. Of those HBVac recipients who were seronegative before vaccination, 79% had a specific anti-HBs response without any side effects. As this vaccine is safe and immunogenic in neonates, it is possible to use it for the prevention of mother-to-infant transmission of HBV.

Hepatitis B vaccine: further studies in children with previously acquired hepatitis B surface antigenemia.

Three doses of inactivated hepatitis B vaccine were given at 1-month intervals to 31 hepatitis B surface antigen (HBsAg)-positive Senegalese children aged between 3 and 24 months. A control group of 18 HBsAg-positive Senegalese children received diphtheria-tetanus-polio vaccine. Immunization of HBsAg-positive infants with hepatitis B vaccine was safe but inefficient. After a 12-month follow-up, the prevalence of HBsAg chronic carriers was not significantly reduced in the hepatitis B vaccine group as compared with the control group: 48.4 and 66.7%, respectively. The presence of hepatitis B antigen was found to be a major risk factor for HBsAg-positive children to develop a chronic carrier state. The risk of developing an HBsAg chronic carrier state was also related to advancing age at time of enrollment in the study.

EFFICACY OF HEPATITIS B VACCINE IN PREVENTION OF EARLY HBsAg CARRIER STATE IN CHILDREN: Controlled Trial in an Endemic Area (Senegal)

Three doses of inactivated hepatitis B vaccine were given at one-month intervals to Senegalese children aged less than two years. A control group received diphtheria/tetanus/polio vaccine. Of those HB vaccine recipients who were seronegative before immunisation, 94·5% had a specific anti-HBs response. Anti-HBs of maternal origin did not interfere with the active immunisation. HB vaccine was without ill-effects, irrespective of hepatitis B marker status before immunisation. After twelve months' follow-up, the incidence of the HBsAg carrier state was reduced by 85% in susceptible children (p<0·0001).