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Biomedical subjects

A Safary

Publications and source records attributed to A Safary.

At least 19 recordsLinked to original sources
PubMed1992

Clinical trial with inactivated hepatitis A vaccine and recommendations for its use.

OBJECTIVE: To compare the reactogenicity and immunogenicity of an inactivated hepatitis A vaccine in two different immunisation schedules. DESIGN: Randomised trial. SETTING: One London teaching hospital. SUBJECTS: 104 healthy adult volunteers (71 men, 33 women aged 19-60). INTERVENTIONS: Hepatitis A vaccine to group 1 (54 volunteers) at 0, 1, and 2 months and to group 2 (50) at 0, 1, and 6 months. MAIN OUTCOME MEASURES: Symptoms at and after each dose; liver function, hepatitis A virus specific serum immune response; and responses in saliva and parotid fluid in immunised volunteers and subjects with natural immunity. RESULTS: The vaccine was well tolerated; 97% (96/99) and 100% of those immunised developed serum antibody after one and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose and were significantly higher in men but not women in group 2 after the third dose (ratio between geometric mean titres 0.265, 95% confidence interval 0.18 to 0.39; p less than 0.001). At one year this group-sex interaction was absent; geometric mean titres for both sexes were significantly higher in group 2 (ratio 0.330, 0.227 to 0.478; p less than 0.0001). Antibody responses were not significantly different between the groups at two years. Compared with naturally infected subjects immunised volunteers developed poor or undetectable virus specific IgG and IgA responses in saliva and parotid fluid. CONCLUSIONS: The vaccine was safe and highly immunogenic, and the differences in the immune responses in saliva and parotid fluid are unlikely to affect its efficacy.

Adult↗
PubMed1992

Heat stability of a recombinant DNA hepatitis B vaccine.

The heat stability of a recombinant DNA hepatitis B vaccine was studied in healthy adult volunteers. When compared with vaccine stored at 4 degrees C, heating of the vaccine for 1 week at 45 degrees C or for 1 month at 37 degrees C did not alter the reactogenicity or the ability of the vaccine to elicit antibody titres considered to be protective. These results have significance in situations where the cold chain is broken, as can happen in countries where proper storage and transport facilities are not always available.

Adolescent↗
PubMed1992

Effect of virus strain and antigen dose on immunogenicity and reactogenicity of an inactivated hepatitis A vaccine.

A randomized double-blind comparison of five killed hepatitis A vaccine preparations was carried out with eligible medical student and staff volunteers. Vaccines were prepared in M RC-5 cells and formalin-inactivated. Three monthly injections of 1 ml in the deltoid muscle were given. Group A received the CLF strain at a dose of 360 ELISA units (El.U) in 0.5 mg aluminium hydroxide (n = 35). The other groups received the HM175 strain as follows: 180 El.U in 1 mg aluminium hydroxide (to group B, n = 42), 360 El.U in 0.5 mg aluminium hydroxide (to group C, n = 40), 360 El.U in 1 mg aluminium hydroxide (to group D, n = 39) and 720 El.U in 1 mg aluminium hydroxide (to group E, n = 43). The geometric mean anti-HAV concentration (GMC) measured in mIV/ml by an ELISA method one month after each injection were: group A, 223, 480, 1635; group B, 123, 221, 649; group C, 185, 365, 1085; group D, 144, 323, 1076; group E, 229, 646, 2521. At month 6, the GMC had fallen by approximately 20%. Seroconversion as measured by ELISA was 100% in groups A and E after one injection, and 100% in all groups after three injections; after two injections, only one subject in group C was still negative. The dose effect with HM175 vaccine was significant. There was a good correlation between ELISA and neutralization (radioimmunofocus inhibition test) titres. One month after the second dose, all subjects in groups A and E had both hepatitis A virus immunoglobulin M (HAV IgM) geometric mean titre, (GMT > 5000) and IgG (GMT > 25,000) as measured by a sensitive terminal dilution ELISA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effect of hepatitis A vaccination schedules on immune response.

An inactivated hepatitis A vaccine was given to 104 seronegative volunteers aged between 19 and 60 years according to two schedules: 0, 1 and 2 months or 0, 1 and 6 months. The vaccine was well tolerated and 97 and 100% of vaccinees developed a serum antibody response following a single and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose; responses following the 0, 1, 6 month schedule were significantly higher at one year but, among those tested at two years, these differences were less marked. Vaccinees, when compared with naturally infected persons, developed poor or undetectable hepatitis-A-virus-specific immunoglobulin G and A antibody responses in saliva and parotid fluid. Such differences are, however, unlikely to affect the protective efficacy of the vaccine.

Adult↗
PubMed1992

Persistence of vaccine-induced antibody to hepatitis A virus.

A level of 10 mIU hepatitis A antibodies/ml as measured by ELISA is believed to be the minimal protective concentration. If this level is considered, the mean persistence of vaccine induced antibodies is approximately 10-11 years after booster dose, 6-7 years if only the primary doses are given and 5-6 years if the minimal individual titre is taken into account.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Simultaneous passive and active immunization against hepatitis A.

The serum antibody response to simultaneous administration of immune globulin (Ig) and an inactivated hepatitis A vaccine was investigated in healthy volunteers who had been tested and found free of hepatitis A virus. One hundred and forty nine subjects were randomly allocated into three groups. Group 1 received three doses of hepatitis A vaccine at 0, 1 and 6 months, group 2 received 5 ml of Ig and group 3 received a combination of Ig and vaccine. In group 3 the seropositivity rate measured by enzyme-linked immunosorbent assay was 100% at day 5, month 1 and 2, 96% at month 6 and again 100% at month 7. In the group that received vaccine alone the seroconversion rates were 0, 96, 100, 98 and 100 respectively. The geometric mean titres in subjects who received passive/active immunization were about twofold lower than in subjects who received vaccine alone, indicating interference of Ig with the immune response. Despite this, the data show that simultaneous administration of hepatitis A vaccine and Ig confers both immediate protection via Ig administration and long-term vaccine-induced protection. As the antibody levels reached are about twofold lower compared to that after administration of hepatitis A vaccine alone, a booster dose may be required sooner, than if the vaccine were administered alone.

Adult↗
PubMed1992

Simultaneous vaccination against hepatitis A and B: results of a controlled study.

Hepatitis A and hepatitis B are endemic in many countries and must be considered as serious health risks for large parts of the world population. Simultaneous or combined vaccination against these two diseases would therefore be most advantageous. In order to investigate possible interactions between these vaccines with respect to their tolerability and immunogenicity, we conducted a randomized prospective study comparing single and simultaneous administration of the two vaccines. Three groups of healthy volunteers, each with 55 persons, were included in the study. All were negative for hepatitis A and hepatitis B markers and had normal serum liver enzyme values. Group I received hepatitis A vaccine (720 ELISA units) into the left deltoid muscle, group II received hepatitis B vaccine (20 micrograms) into the right deltoid muscle and group III received hepatitis A vaccine into the left, and hepatitis B vaccine into the right deltoid muscle. Three doses of the vaccines were administered at 0, 1 and 6 months. Local and systemic reactions were monitored by means of questionnaires. Blood samples for determination of antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen (anti-HBs) and of serum SGOT and SGPT levels were drawn at months 0, 1, 2, 6 and 7. There were no serious general and only mild local reactions. The mean serum SGOT and SGPT values remained in the normal range in all groups. The seroconversion rates and mean geometric titres of the anti-HAV and anti-HBs antibodies were similar when the vaccines were administered separately or simultaneously. There were no significant differences between the compared groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings.

The objectives for the clinical testing of the inactivated hepatitis A vaccine developed by SmithKline Beecham Biologicals are reviewed and the results obtained are summarized. The first studies were carried out in healthy young adult volunteers using pilot vaccine lots prepared from the CLF and HM175 strains of hepatitis A virus (HAV). It was established that the candidate vaccines were well-tolerated, caused no hypersensitivity reactions and elicited a strong antibody response. As the yield in production with the HM175 strain was higher it was preferred over the CLF strain for further development of a vaccine. A dose-range study with HM175 vaccine in adults showed that an antigen dose of 720 ELISA units (El.U) produced almost 100% seroconversion after one injection. This dose was therefore chosen as appropriate for adults. A dose of 360 El.U was used in children. To date, a total of 67 studies in 18 countries involving 47,145 subjects, including 20,586 control subjects, have been initiated. In these studies, 55,259 doses of HM175-derived hepatitis A vaccine have so far been administered. This extensive experience has shown that the vaccine is well-tolerated, causing essentially only mild, transient local reactions. Vaccine reactogenicity was assessed using symptom checklists, filled in by the volunteers or their parents, for a period of 4 days following vaccination. Blood samples were obtained at different times after vaccination to evaluate the immune response. Clinical studies with six different lots, manufactured using commercial-scale production methods, have been carried out on 2901 adults. These studies have shown that a seroconversion rate of 95.7% (1225/1280) is obtained one month after the first vaccine dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Long term efficacy of hepatitis B vaccine in infants born to hepatitis B e antigen-positive mothers.

The long term protective efficacy of recombinant hepatitis B vaccine, administered alone or concomitantly with hepatitis B immunoglobulin, was assessed in 263 healthy neonates of hepatitis B e antigen-positive mothers. Infants received the first dose of vaccine at birth; additional doses were given at either Months 1, 2 and 12 or Months 1 and 6. During the follow-up period, which ranged from 2 to 4 years, protective titers (> or = 10 mIU/ml) of anti-hepatitis B surface antibodies were found in virtually all infants who had responded to the primary course of vaccination. "Natural boosts," without persistent infection, were observed in only a small number of children. All children who were shown to have become chronic carriers were infected within the first year of life. No statistical difference in long term protective efficacy could be shown between the two vaccination schedules used or between the use of vaccine alone or vaccine plus hepatitis B immunoglobulin for either schedule.

Cohort Studies↗
PubMed1991

The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers.

Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination.

Carrier State↗
PubMed1990

Safety and immunogenicity of an inactivated hepatitis A candidate vaccine in healthy adult volunteers.

The reactogenicity and immunogenicity of a formaldehyde-inactivated hepatitis A vaccine have been investigated. Three different dose levels of vaccine (180, 360 and 720 ELISA units) were administered to healthy volunteers according to a 0, 1, 2 and 12 month schedule. The vaccine was safe and well tolerated. Reactions observed following vaccination were essentially mild and were not dependent upon the quantity of antigen administered. All subjects had measurable titres of anti-HAV antibodies after the full vaccination course; the immune response to the vaccine was dose-related. Antibody titres in vaccinees at month 13 were between 60- and 190-fold higher than those observed in a group of subjects given anti-HAV immunoglobulin.

Adolescent↗
PubMed1989

Protective efficacy of a recombinant deoxyribonucleic acid hepatitis B vaccine in institutionalized mentally handicapped clients.

Mentally handicapped clients in institutions are at high risk for hepatitis B virus (HBV) infection. In 1985, 770 mentally handicapped residents from four institutions in the Antwerp area were screened for HBV markers. The prevalence of hepatitis B surface antigen was 10.3 percent (range, 6.1 to 15.2 percent); 42.3 percent (range, 11.5 to 60.1 percent) had antibodies to hepatitis B surface antigen and the hepatitis B core antigen. In 1986, 275 seronegative mentally handicapped residents were vaccinated intramuscularly in the deltoid region with 20 micrograms (1.0 ml) of a recombinant deoxyribonucleic acid yeast-derived hepatitis B vaccine (Engerix-B, SmithKline Biologicals, Rixensart, Belgium) on a zero-, one-, six-month schedule. Serum samples were collected at Months 1, 2, 7, 12, and 24 and were tested for HBV markers by radioimmunoassay. The seroconversion rates for hepatitis B surface antigen antibodies were 39 percent at Month 1 (geometric mean concentration, 6.4 IU/liter), 82 percent at Month 2 (geometric mean concentration, 23.4 IU/liter), 97 percent at Month 7 (geometric mean concentration, 1,034 IU/liter), and 96 percent at Month 12 (geometric mean concentration, 269 IU/liter). Among the 214 residents evaluated at Month 12, 69 percent had hepatitis B surface antigen antibody levels greater than 100 IU/liter (geometric mean concentration, 603 IU/liter). No significant adverse reactions were observed. Within the first seven months of observation, HBV infection was detected in eight of 271 subjects (estimated annual incidence of 5 percent). During this period, none of the clients developed clinical hepatitis or showed biochemical evidence of liver damage. Between eight and 24 months, no additional HBV infections were detected. These data can be compared with an annual incidence of HBV infection of 8.7 percent in a historical cohort of mentally handicapped residents in one of the four institutions.

Adolescent↗
PubMed1989

Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers.

We have assessed the protective efficacy of a recombinant DNA hepatitis B vaccine alone in infants of women who were positive for the surface antigen and the e antigen. The infants received a 10-micrograms dose of the vaccine within 12 hours of birth and additional doses 1, 2, and 12 months later. No significant adverse reactions to vaccination were observed and the vaccine was highly immunogenic. Only 2 (3.6%) of the 55 infants followed up to 13 months became chronically infected with the hepatitis B virus, as evidenced by the persistent presence of hepatitis B surface antigen in serum samples. Without immunoprophylaxis, 65% to 90% of such infants would become chronic carriers. Immunization with a recombinant vaccine without concomitant administration of hepatitis B immunoglobulin, therefore, considerably decreased the incidence of the carrier state.

Carrier State↗
PubMed1988

Lack of induction of IgE and IgG antibodies to yeast in humans immunized with recombinant hepatitis B vaccines.

Yeast-derived hepatitis B vaccines (partially purified or highly purified) at different dosages and a plasma-derived hepatitis B vaccine (control) were injected into 50 young volunteers 3 times at monthly intervals. Before and 4 weeks after this series of immunizations, blood samples were drawn and tested for presence of IgE and IgG antibodies against yeast antigens. No rise in IgE antibodies against Saccharomyces cerevisiae antigens nor in IgG antibodies against Candida albicans antigens was found. Together with former clinical results this underlines the experience that type I and type III reactions against putative yeast contaminants apparently play no major role after immunization with recombinant hepatitis B vaccines.

Adult↗
PubMed1987

Clinical development of a new recombinant DNA hepatitis B vaccine.

The clinical development plan for the new recombinant DNA yeast-derived hepatitis B vaccine manufactured by SmithKline Biologicals is summarized. Initially, the emphasis was on assessing the risk of hypersensitivity to yeast-derived contaminants. This was followed by an evaluation of local and general reactions after vaccination. Next, the optimal dose of vaccine to be administered was ascertained followed by an evaluation of the efficacy of different vaccination schedules. The reactogenicity and immunogenicity of the yeast-derived vaccine was compared with that of two commercially available plasma-derived vaccines. The recombinant vaccine's protective efficacy was assessed in chimpanzees and by comparing attack rates in historical homosexual control groups with those in vaccinated homosexuals. Ongoing studies are investigating the protection of neonates born to HBeAg-positive carrier mothers.

Antigens↗
PubMed1987

Reactogenicity and immunogenicity of different lots of a yeast-derived hepatitis B vaccine.

Several lots of a yeast-derived hepatitis B vaccine at different doses and a 20 micrograms dose of plasma-derived vaccine were tested in young healthy adults and compared with respect to risk of hypersensitivity reactions, reactogenicity, and immunogenicity. No signs of hypersensitivity either pre-existing or vaccine-induced were observed. Reactogenicity was low and similar in all vaccine groups. It was not dose related and unaffected by the number of injections. Immunogenicity was evaluated for a 0, 1, 2, and 12 month vaccination schedule. Seroconversion rates (greater than or equal to 10 IU/l) were not significantly different between the purified yeast- and plasma-derived vaccines one month after the second vaccination whereas the percentage of seroconversion was slightly lower in the groups receiving only partly purified recombinant vaccines. Although geometric mean titres induced by the plasma-derived vaccine were somewhat higher after the first months, the antibody titres induced by the recombinant vaccine were at least as high as those elicited by a plasma-derived vaccine following the booster dose.

Antigens↗
PubMed1987

Persistence of vaccine-induced antibodies to hepatitis B surface antigen and the need for booster vaccination in adult subjects.

Protection against hepatitis B virus infection can be achieved by the induction of neutralizing antibodies against the hepatitis B surface antigen (HBsAg). An antibody concentration of 10 IU/l, as measured by radioimmunoassay, is considered to be protective. HBsAg can be produced either from the plasma of chronic carriers or by DNA recombinant technology in yeast cells. Plasma- and yeast-derived vaccines have been compared in several studies and their immunological properties were found to be similar, including the persistence of antibodies induced by either type of vaccine. Finally, yeast-derived hepatitis B vaccine can boost anti-HBs responses initially elicited by either plasma- or yeast-derived vaccine equally and effectively. In order to maintain protective immunity after hepatitis B vaccination, antibody determination and, if necessary, booster vaccination should be performed, particularly in high-risk persons.

Adult↗