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Biomedical subjects

R Sänger

Publications and source records attributed to R Sänger.

At least 19 recordsLinked to original sources
PubMed2006

Booster immunization with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate combination vaccine in the second year of life: safety, immunogenicity and persistence of antibody responses.

The immunogenicity and reactogenicity of booster vaccination with GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine was assessed in toddlers aged 12-18 months previously primed with the same combination (N=341), or with DTPa-IPV/Hib and HBV administered separately (N=102; Trials 217744/059 and 217744/096). Antibody persistence at age 4-6 years was also assessed in children who had received a 4th consecutive dose of DTPa-HBV-IPV/Hib vaccine or separate DTPa-IPV/Hib and HBV vaccines in this study and in another study conducted under similar conditions in Germany. Prior to booster vaccination in the second year of life, antibody concentrations and seroprotection rates were similar irrespective of the primary vaccine used. One month after boosting with DTPa-HBV-IPV/Hib, substantial antibody increases were observed against all vaccine antigens indicative of previous immune priming. Seropositivity and booster response rates against all antigens were 97.4-100%. Reactogenicity following booster vaccination with DTPa-HBV-IPV/Hib was similar regardless of the primary regimen used. Three to four years after administration of the 4th DTPa-HBV-IPV/Hib dose, >90% vaccinees had persistent protective antibody concentrations against diphtheria, hepatitis B, Hib and the three poliovirus types. Anti-tetanus antibody concentrations were > or = 0.1 IU/ml in 76.4% subjects and seropositivity for pertussis antibodies ranged from 34.5% for PT to 98.9% for FHA. In conclusion, the combined hexavalent DTPa-HBV-IPV/Hib vaccine is immunogenic and safe when used for boosting in the second year of life, regardless of the primary vaccine used, and offers sustained protection during early childhood and beyond.

Child↗
PubMed2006

Assessment of nine candidate DTP-vaccines with reduced amount of antigen and/or without adjuvant as a fourth (booster-) dose in the second year of life.

BACKGROUND: The incidence of local reactions to diphtheria-, tetanus and acellular pertussis (DTaP-) vaccines in infants and toddlers increases with each subsequent dose, and entire thigh swellings (ETS) have been reported. Lowering the amount of antigen or of adjuvant may decrease the reactogenicity of DTaP while maintaining a protective immune response. OBJECTIVES: Following priming with three doses of a DTaP vaccine during infancy, the safety, reactogenicity and immunogenicity of nine different candidate DTaP-vaccines with reduced amounts of antigen and/or adjuvant given as fourth (booster) dose were evaluated. METHODS: Study participants were healthy infants aged 15-27 months at the time of booster vaccination. Each participant had received three doses of a DTaP vaccine (Infanrixtrade mark, GlaxoSmithKline, Rixensart, Belgium; "reference DTaP") at age 3, 4, and 5 months as part of a previous clinical trial. More than 20,000 children were eligible for participation in the current study protocol at the time. In a first phase at a University hospital-based vaccination study center, nine sequential cohorts of 63-119 study subjects received one of nine different candidate vaccines. Patients and study personal were blinded with regard to which vaccine was currently in use. Reactogenicity was solicited from parents using diary cards. Blood was drawn prior to and 4 weeks after vaccination and immediately centrifuged. The serum was stored at -20 degrees C until serology was performed by ELISA tests. As soon as the first candidate vaccine with adequate reactogenicity and immunogenicity profile was identified in the first study phase, a second study phase was initiated in parallel, to evaluate the safety and reactogenicity of the respective candidate vaccine in private practices in large cohorts (1613-2095 study subjects per group). RESULTS: In the first study phase, DTaP with no aluminum induced the highest frequency of ETS and fever. All other candidate vaccines caused lower rates of local and general reactions than the reference DTaP. As a general rule, vaccines with less antigen induced fewer reactions, although there was no strict dose-response effect and the difference, e.g. between a one-tenth and a one-fifth DTaP dose (DTaP 1/5; DTaP 1/10) was not clinically relevant. Separate injections of Td and aP caused fewer general reactions than the respective TdaP combination and local reactions were higher at the aP than at the Td injection site. Again, as a general rule, reduced amounts of antigen induced lower antibody concentrations, although all vaccines induced "protective" anti-tetanus and anti-diphtheria antibody responses. A total of 92-100% of children showed seroresponses to pertussis antigens even when vaccinated with reduced amounts of the respective pertussis antigen. Elimination of aluminum from DTaP vaccine induced higher anti-tetanus-antibody concentrations and so did a reduction of the amount of diphtheria antigen. Additional examples for antigen interaction were increased antibody concentrations, observed with injection of Td and aP into different limbs. In the second study phase, all three vaccines evaluated (one with a reduced amount of diphtheria antigen, TdaP; one with reduced amounts of all antigens, tdap; and one with a fifth dose of the reference vaccine (DTaP 1/5)) were safe and had an acceptable reactogenicity profile in a total of 4871 study subjects. CONCLUSIONS: Local reactions due to DTaP booster doses in the second year of life can be reduced by reducing the amount of antigen in the respective vaccine while an adequate immunogenicity is maintained. Aluminum-free vaccines induced ETS and fever most commonly. Any changes in vaccine composition should lead to a full evaluation of the new product.

Adjuvants, Immunologic↗
PubMed2005

Cell mediated and antibody immune response to inactivated hepatitis A vaccine.

The humoral and cellular immune response to inactivated hepatitis A vaccine was investigated dynamically in a time elapse study over 1 year. Fourty-five healthy volunteers, seronegative for anti-HAV, were vaccinated with 1440 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus following a 0--6-month schedule. Serum anti-HAV levels and HAV-specific proliferation of peripheral blood mononuclear cells were measured at several time points over a 26- and 28-week period after the first and second injection, respectively. Distinct B and T cell responses were determined within 14 days after primary vaccination. The booster vaccination-induced immediate peak levels for the humoral (anti-HAV GMC=5376mIU/ml) as well as the cellular (median Deltacpm=14173cpm) response.

Adult↗
PubMed2005

Comparison of the immunogenicity and reactogenicity of two commercially available hexavalent vaccines administered as a primary vaccination course at 2, 4 and 6 months of age.

Infants (N = 459) were randomly assigned to receive either Infanrix hexa or Hexavac vaccines at 2, 4 and 6 months of age as a primary vaccination schedule. The immunogenicity of the hepatitis B component was statistically significantly higher for Infanrix hexa compared to Hexavac in terms of both seroprotection (98.6% versus 94.7%, p = 0.0302) and GMCs (905.6 versus 226.4, p < 0.0001). Significantly (p < or =0.0001) higher antibody levels against diphtheria and the 3 polio components were also induced by Infanrix hexa. The responses to tetanus, Hib and pertussis components were similar. The incidences of clinically relevant solicited symptoms, unsolicited symptoms or serious adverse events were low in both groups.

Antibodies, Bacterial↗
PubMed2004

Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants.

Safety, reactogenicity and immunogenicity of GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix)hexa) was assessed when used for primary vaccination at 3, 4 and 5 months of age (N = 2163), compared to the separate administration of DTPa-IPV/Hib and HBV vaccines (N = 720). A similar safety and reactogenicity profile was demonstrated for both vaccine regimens, as well as a good immune response for all antigen components. By offering protection against six diseases in a series of single injections, the hexavalent DTPa-HBV-IPV/Hib vaccine was shown to be a safe, well tolerated and immunogenic alternative to primary immunization with licensed separately administered vaccines.

Bacterial Capsules↗
PubMed2002

Pandemic preparedness: lessons learnt from H2N2 and H9N2 candidate vaccines.

Vaccination against influenza is considered to be one of the key interventions in case of a pandemic. Unfortunately, shortages in vaccine supplies will occur because of the substantial increase in vaccine demands worldwide and the limited available supply resources. The recommended use of monovalent--instead of current trivalent--vaccines containing 15 micro g hemagglutinin (HA) per dose can theoretically triple vaccine volumes but is unlikely to meet the demand. Furthermore, previous experiences demonstrated that one dose of 15 micro g HA will not be sufficient to elicit protective antibody levels in unprimed individuals. Modified formulation approaches were investigated, that would be suitable to provide significantly higher volumes of potent vaccine within a given period of time. Low doses of HA combined with aluminum (Al) adjuvants and the use of whole virus instead of split or subunit antigens can lead to substantial increases in process yield. In addition, production of whole virus vaccines will reduce manufacturing complexity. In a dose-finding study in healthy adults and elderly, immune responses after administration of Al-adjuvanted low-dose formulations were compared to a standard split virus vaccine (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium). All vaccines were safe and well tolerated. Antigen concentrations as low as 1.9 micro g HA/strain per dose of adjuvant-containing experimental vaccines induced protective antibody levels in primed populations. Reactogenicity profiles of Al-adjuvanted low-dose vaccines were investigated in a feasibility trial. Neither the use of Al-adjuvant nor of whole virus had a significant effect on general reactions. Studies in unprimed populations with H2N2 and H9N2 candidate vaccines showed different results, with a potential need for a two-dose schedule. Indeed, hemagglutination inhibition titers did not reach protective levels after a single vaccine dose but could be met following administration of a second dose. The same is true for Al-adjuvanted whole virus formulations with an up to eightfold-reduced antigen content. It may be concluded that the use of Al-adjuvanted whole virus vaccines with low HA content can raise protective antibody levels after two vaccine doses, which may, in turn, result in significant increases of vaccine supplies in the case of a pandemic.

Adjuvants, Immunologic↗
PubMed2002

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.

Adolescent↗
PubMed2000

Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course?

A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in Germany since 1997. We investigated possible differences in immunogenicity and safety when changing over from vaccinations with monovalent vaccines made by different manufacturers to vaccinations with the combined hepatitis A/B vaccine in an open, randomized, multicenter trial. We therefore compared four different schemes changing over from concomitant vaccinations with monovalent vaccines against hepatitis A and B (Havrix 1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined vaccination against hepatitis A+B with three injections of the combined hepatitis A/B vaccine (0, 1, and 6 month schedule). Local and general symptoms were mostly mild in all five groups. With complete three-dose course using the combined vaccine or an early changeover from monovalent vaccines to the combined vaccine, higher overall anti-HBs seroprotection rates and geometric mean concentrations (GMCs) against hepatitis B could be achieved as early as after 2 months as compared to those groups switching later to the combined vaccine. This study demonstrated for the first time that switching from monovalent hepatitis A and B vaccinations to the combined hepatitis A and B vaccination has no negative influence on the tolerability and improves the immunogenicity.

Adolescent↗
PubMed2000

Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virus- inactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections.

OBJECTIVE: The aim of this open, multicenter, randomized trial was to evaluate the immunogenicity and reactogenicity of a candidate combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus (DTaP-HBV-IPV) vaccine when given as either a mixed or as separate concomitant injections with Haemophilus influenzae type b (Hib) vaccine. STUDY DESIGN: A total of 359 subjects were randomized to receive either DTaP-HBV-IPV/Hib (mixed administration - 180 subjects) or DTaP-HBV-IPV + Hib (separate administration in opposite limbs - 179 subjects) at 2, 3, and 4 months of age. RESULTS: After vaccination, seroprotective antibody concentrations against diphtheria, tetanus, hepatitis B, and polio viruses and a high (> or = 97%) pertussis vaccine response were seen in almost all study participants. All subjects except one in the mixed administration group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15 microg/mL. Of subjects in the mixed and separate group, 77.2% (geometric mean antibody concentration, 2. 62 microg/mL) and 88.6% (geometric mean antibody concentration, 4.45 microg/mL) had Hib anti-PRP concentrations > or = 1 microg/mL, respectively. The addition of the Hib component to the 5-component vaccine did not increase the incidence of local or general reactions. CONCLUSION: Both administrations of the candidate vaccine were found to be safe, immunogenic, and well tolerated. Although anti-PRP geometric mean antibody concentrations and the percent of subjects achieving the 1 microg/mL seroprotective level were lower after the mixed administration, they were in the range seen with monovalent Hib vaccines or with other DTaP-based/Hib combinations licensed in some European countries. Therefore both administrations have the potential to simplify childhood immunization.

Antibody Formation↗
PubMed1998

The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg.

Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiveness to HBsAg vaccination was associated with DRB1*3 and DRB1*7. In addition, DRB1*13 was significantly increased among vaccine responders (35.2% vs 5.4%;p < 0.0001) suggesting an immune response promoting effect for this allele whereas the closely related allele DRB1*14 was associated with nonresponse in the infant study. There was no evidence for a hole in the T cell receptor Vbeta repertoire. In conclusion, in agreement with results obtained in mice there appears to be a hierarchy of DRB1* genes in the HBsAg immune response. The possible differential association of DRB1*13 and DRB1*14 may allow the identification of differences between responsiveness and nonresponsiveness to a few amino acid differences in the beta1-domain of the class II heterodimer.

Adult↗
PubMed1997

Booster immunization of low- and non-responders after a standard three dose hepatitis B vaccine schedule--results of a post-marketing surveillance.

Seventy-nine low-responders and 83 non-responders after a previous three-dose hepatitis B (HB) vaccine course at 0.1, and 6 months were enrolled to receive additional 20 micrograms recombinant HB vaccine doses every 2 months until all had anti-HBs levels > or = 100 mIU ml-1. After the first booster, 65.4% had anti-HBs levels > or = 100 mIU ml-1, 17.9% were low-responders (10-99 mIU ml-1), and 16.7% remained non-responders (< 10 mIU ml-1). All complying non-responders developed anti-HBs levels > or = 100 mIU ml-1 after the third booster at the latest, whereas all low-responders reached this level after the second booster. Although body mass index affected the response to the first hepatitis B booster, when full compliance to regular revaccination was ensured, all non- and low-responders eventually reached sufficient anti-HBs levels.

Adolescent↗
PubMed1996

Immunogenicity of a recombinant hepatitis B vaccine in adults.

OBJECTIVES: To evaluate the immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in health care staff under routine use and unselected conditions and to investigate factors that influence the response to vaccination. METHODS: This prospective postmarketing surveillance study was performed in unselected health care staff and their relatives (age range, 12-60 years) at 58 hospitals. Overall, 880 subjects were administered a 20-microgram dose of a vaccine at 0, 1, and 6 months according to the prescribing information and under routine hospital practice, and they were tested for antibody to hepatitis B surface antigen after the third dose at the hospitals routine laboratory. The principal outcome measures were antibody to hepatitis B surface antigen titers that were expressed as the seroprotection rate (SPR) (SPR [given as a percentage], > or = 10 mlU/ mL), spontaneously reported adverse events, and geometric mean titers (in milli-international units per milliliter). RESULTS: The compliance to the 3-dose schedule under routine hospital practice was 98.1%. The immune response was good in all age groups, and the overall SPR was 97.8% at 1 month after the third dose in field conditions with unselected health care workers. The SPR in vaccinees (age range, 40-59 years) was close to 95%. Age (P < .001), smoking (> or = 10 cigarettes per day) (P < .001), Broca index (> 110%) (P < .001), antibody to hepatitis B surface antigen testing (> 8 weeks after the last dose) (P = .03), chronic underlying disease (P = .04), and male gender (P = .04) were factors associated with lower geometric mean titers in routine vaccine use. No serious adverse events were reported. CONCLUSION: The large immune response that was elicited by this hepatitis B vaccine in adults under daily routine field conditions reflected reality, with a high SPR also found in elderly and other persons with risk factors associated with a lower immune response.

Adolescent↗
PubMed1995

Accelerated Schedule for Hepatitis B Immunization.

Background: A considerable number of people remain unprotected against hepatitis B. These people may require immunization at short notice before being exposed to situations or locations where a risk of infection is present. Currently, full active immunization against hepatitis B, when administered according to recommended schedules, takes 2-6 months. This open, randomized multicentric study evaluated the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine in adults when it was administered according to three different rapid vaccination schedules. Methods: Five hundred and twenty four healthy adults (aged 18-59 years) were randomly divided into three groups. Hepatitis B vaccine was given intramuscularly in the deltoid muscle at months 0, 1, and 2 (group A); weeks 0, 14, and 28 (group B); and weeks 0, 7, and 21 (group C). Symptoms were recorded by the subjects on individual diary cards. AntiHBs were measured using radioimmunoassay (Ausab-Abbott); a seroprotective titer was defined as 10 IU/L. Results: At day 28, no significant difference in seroprotection rates (SPRs) i.e., seroconversion >= 10 IU/L,was observed, between groups B (55.6%) and C (65.2%), but both these groups had significantly greater SPRs than group A (15.0%). Although not significant (p=.07), groups B and C also had higher SPRs than group A (78.5% and 76.4% versus 65%) at day 56. One month after completing the three dose schedules, the SPRs were as follows: 89.0% (group A); 78.5% (group B); and 76.4% (group C), increasing to > 94% at month 7 to 8 in all three groups. The SPRs at month 13 were 95.8%, 98.9%, and 98.6%, respectively. Among the three groups, no significant differences were observed from month 2 onwards in either SPRs or geometric mean titers. In groups A, B, and C, 3.7%, 5.0%, and 7.1% of the vaccine injections were associated with local symptoms. Also 8.3%, 6.2%, and 6.3% of subjects exhibited general symptoms following each vaccine dose; all symptoms were transient and resolved spontaneously. Conclusions: This recombinant hepatitis B vaccine administered at weeks 0, 7, 21, or at weeks 0, 14, 28, rapidly elicits high rates of seroprotection, which persist at least until month 12.

Journal Article↗
PubMed1992

[Short term cultivation of Plasmodium for the determination of chloroquine resistance].

The in-vivo-test of Plasmodium drug resistance is one of the essential basic controls, assisting therapeutic measures in tropical malaria. An initial in-vitro-check up of drugs provided for antimalarial therapy is another useful help to the clinician. Even when manufactured WHO test kits are not available, the analysis of drug resistance can be performed under simple working conditions. Its application is demonstrated in a patients history.

Animals↗
PubMed1980

[Hemobilia after Menghini puncture].

In 100 patients before and after a percutaneous blind puncture of the liver after Menghini biliary juice was received with the help of a duodenal sound and this was investigated for blood admixtures microscopically and chemically. In 21 out of 100 punctures patients blood was proved in the duodenal juice: In 11 cases the proof of blood was positive before and after the puncture and in 10 patients only after the puncture blood was found in the duodenal juice. A macrohaemobilia was never observed. The influence of thromboplastin time, number of thrombocytes, time of haemorrhage, age and basic disease on the development and support of microhaemobilia was examined. In about 10% of the patients is to be reckoned with a microhaemobilia taking into consideration the indication and contraindication, also in exact performance of the blind puncture of the liver. However, the clinical importance is little in general.

Adult↗