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Biomedical subjects

R M Jacobson

Publications and source records attributed to R M Jacobson.

At least 37 records · Page 2Linked to original sources
PubMed1999

An acellular pertussis vaccine in healthy adults: safety and immunogenicity. Pennridge Pediatric Associates.

Recent data indicate that Bordetella pertussis can be an important cause of illness in adolescents and adults. In a randomized observer- and subject-blinded study, adults (> or = 18 years of age) received an acellular pertussis (aP) vaccine containing genetically inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), or a saline placebo, and were monitored for safety and immunogenicity. IgG antibodies to PT, FHA, and PRN were measured by enzyme-linked immunosorbent assay (ELISA) and PT neutralization by a Chinese hamster ovary (CHO) cell assay. Local reactions, more common in the aP group, were mild and transient. One month after immunization, geometric mean ELISA antibody concentrations for the aP and placebo groups, respectively, were: anti-PT, 463 and 7.6; anti-FHA, 417 and 18; and anti-PRN, 855 and 14. The anti-PT neutralization titers for the aP and placebo groups were 1:3439 and 1:58 respectively. This aP vaccine is a safe and immunogenic candidate booster vaccine against pertussis for adults.

Adolescent↗
PubMed1999

A randomized, controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant.

The safety and immunogenicity of a novel hepatitis B virus (HBV) vaccine containing recombinant PreS2 and S antigens combined with MF59 adjuvant (HBV/MF59) was evaluated in healthy adults (N=230) who were randomized to receive 2 or 3 immunizations of either the study vaccine or a licensed control vaccine (Recombivax HB). After a single immunization, 105 of 118 (89%) recipients of HBV/MF59 achieved protective serum levels of anti-HBs antibody (> 10 mIU/ml), compared with 13 of 110 (12%) recipients of licensed vaccine (P < 0.001). The geometric mean titer (GMT) after 2 doses of HBV/MF59 given 2 months apart (13,422 mIU/ml) was more than 5-fold higher than that following 3 doses of licensed vaccine given over 6 months (2,346 mIU/ml; P < 0.001). The GMT following 3 injections of HBV/MF59 (249,917 mIU/ml) was 100-fold higher than licensed vaccine (P < 0.001). Anti-PreS2 antibodies were elicited in over 90% of the subset of HBV/MF59 recipients tested. Both vaccines were well tolerated; transient, mild-to-moderate local inflammation was the major postinjection reaction.

Adjuvants, Immunologic↗
PubMed1999

Promises and pitfalls of meta-analysis in vaccine research.

Meta-analysis continues to grow in usage despite increased concern regarding its soundness. Over twenty meta-analyses directly pertain to vaccines. Vaccine researchers need to understand the technique as well as the criticisms. Meta-analysis involves four steps. First, the meta-analyst should establish certain criteria in advance of the second step where the meta-analyst gathers the data--the results of the individual studies. Third, the meta-analyst assesses the individual studies for combinability and, fourth, the meta-analyst actually combines the data to generate conclusions. Vaccine meta-analyses have addressed a variety of vaccines and a variety of study objectives including efficacy, immunogenicity and safety. Three classical concerns revolve around the issue of publication bias, data dredging and individual study variability. Additionally, vaccine meta-analyses suffer concerns particular to the field of vaccine research.

Animals↗
PubMed1999

The current status of the rotavirus vaccine.

The US just licensed of an oral tetravalent rhesus reassortant vaccine for routine immunization of infants against rotavirus. The virus was first identified 25 years ago and is now recognized to be the most common single cause of severe diarrhea throughout the world. Most children suffer at least one infection and reinfection is common. Studies of natural immunity show that breastfeeding may merely delay onset of primary infection and that maternal immunity has little effect-especially in developing countries where onset in early infancy is common. Immunity, furthermore, appears to be serotype-specific. Early attempts to develop a vaccine focused on animal forms of rotavirus. More recent efforts have created human-animal reassortants that have been far more successful.

Animals↗
PubMed1999

Measles antibody seroprevalence rates among immunized Inuit, Innu and Caucasian subjects.

Measles antibody seroprevalence was compared in Innu, Inuit, and Caucasian peoples of northern Newfoundland, Canada, who were immunized with a single dose of M-M-R-II (Merck Research Laboratories) vaccine. Healthy, volunteer schoolchildren (n = 606) were enrolled. Measles antibody was measured with a whole virus measles-specific IgG EIA. Native (Innu and Inuit) schoolchildren (n = 253) had a significantly higher seropositive rate (83%) after a single dose of measles vaccine compared to Caucasian (n = 353) children (76%; p = 0.025), and higher mean antibody levels after immunization compared to Caucasian children (1.74 EIA units, vs. 1.63; p = 0.06). Caucasian children were more likely to have been immunized after age 15 months (20.6% vs. 9.6%; p = 0.001). There was no significant difference in the mean time interval between immunization and blood sampling for natives versus Caucasian (8.0 years vs. 7.95 years; p = 0.49). After adjustment for time from immunization and age at immunization, there remained a marginally significant racial difference in seropositivity (OR = 1.65, 95% CI 0.96, 2.83, p = 0.068). The unadjusted odds ratio for seropositivity (comparing natives vs. non-natives, combining negative and equivocal results) was 1.66 (95% CI 1.06-2.59, p = 0.018). The higher measles-seropositive rate found among native compared to non-native Canadian children suggests that genetic and/or environmental factor(s) affect circulating antibody levels following immunization. The determination of these sources of variability may lead to the development of more efficacious vaccines or delivery strategies.

Adolescent↗
PubMed1999

Concurrent administration of inactivated hepatitis A vaccine with immune globulin in healthy adults.

301 healthy adult volunteers were randomized to one of three treatment groups: inactivated hepatitis A vaccine alone; inactivated hepatitis A vaccine with immune globulin (Ig) concurrently; or Ig alone. The first two treatment groups received a second dose of hepatitis A vaccine at week 24. Anti-HAV was measured 4, 8, 12, 24 and 28 weeks after the primary immunization. When comparing subjects receiving inactivated hepatitis A vaccine alone to those receiving vaccine and Ig, the seropositivity rates were not significantly different at 4, 8, 12 and 28 weeks, but at week 24 the seropositivity rate was lower in the group receiving both vaccine and Ig compared to the group receiving vaccine alone (92.0% compared to 97.0%). At weeks 8, 12 and 24 the geometric mean titers (GMTs) were significantly lower for subjects receiving both vaccine and Ig. The GMTs were not significantly different after the second dose of vaccine. At all time points, the lower serum antibody concentrations observed in subjects receiving both inactivated hepatitis A vaccine and Ig were nevertheless substantially higher than the cutoff for assay seropositivity and much higher than after Ig alone; these differences are therefore clinically insignificant.

Adolescent↗
PubMed1999

Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

Adolescent↗
PubMed1998

The association between HLA class I alleles and measles vaccine-induced antibody response: evidence of a significant association.

While the Moraten strain measles vaccine is an excellent, safe, and immunogenic vaccine, vaccine failure occurs, presumably when an individual develops an inadequate immune response. In this study, we examined the association of HLA class I genes and measles vaccine-induced antibody levels. We found that the allele distribution of HLA-B alleles differed between non-responders and hyper-responders (p = 0.002). Several class I alleles were associated with non-response (HLA-B13, -B44, and -C5); whereas several other alleles were associated with hyper-response (HLA-B7 and -B51). In addition, non-responders were more likely to be HLA-B homozygous than normal responders (odds ratio 2.1), and more likely to be homozygous than hyper-responders (odds ratio 3.7, p = 0.031 Mantel-Haenzel for trend). Finally, we found evidence of an allele dose-response phenomenon for HLA-B7. We conclude that there are important associations between class I HLA genes and measles antibody levels following immunization.

Adolescent↗
PubMed1998

The genetic basis for variation in antibody response to vaccines.

Following a brief review of important concepts of vaccine response and vaccine immunology, recent reports on genetic determinants of vaccine response are reviewed. Recent data demonstrating significant associations with particular human leukocyte antigen genes and responsiveness to measles and hepatitis B vaccines are discussed, along with the influence of Km and Gm allotype genes on pneumococcal polysaccharide vaccines. These recent findings have important considerations for research, vaccine development, and clinical practice.

Antibody Formation↗
PubMed1998

The impact of a simulated immunization registry on perceived childhood immunization status.

We developed a simulated immunization registry to assess the impact on the perceived immunization status in a population-based sample of 2-year-olds living in Olmsted County, MN, in 1995. We compiled records of all immunizations by abstracting immunization data from all medical care facilities in the county. The data collected from each facility were analyzed separately to provide the immunization rate as perceived by each facility. This perceived rate was compared to the rate obtained by combining all recorded immunizations from all facilities (simulated registry). Information on children not receiving any carefrom facilities in Olmsted County was compiled from birth certificate data and community school lists. Data from the simulated registry indicated that 69.1% of all children in Olmsted County with medical records were up-to-date on their immunizations by 20 months of age. By 24 months, this increased to 74.2%. The immunization rate of 24-month-old children recorded at individual healthcare facilities in Olmsted County ranged from 24.3% to 79.5%. The addition of data from the simulated registry increased the immunization rate at each site: a 27.7% relative increase in the site with the lowest recorded immunization rate, a 14.0% increase in the site with the intermediate immunization rate, and a 6.9% increase in the site with the highest internally perceived immunization rate. The registry also identified excess immunizations in 5% of the county's 2-year-olds. Each healthcare facility in this community gained an immediate benefit from the development of a simulated immunization registry. This immediate improvement in one quality-of-care measure (up-to-date immunization rate) should be factored into the cost/benefit assessment of immunization registries.

Birth Certificates↗
PubMed1997

Determination of deltoid fat pad thickness. Implications for needle length in adult immunization.

OBJECTIVE: To measure deltoid fat pad thickness and determine the optimal needle length for deltoid intramuscular immunization in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 220 healthy health care workers (126 women, 94 men) at the Mayo Medical Center, Rochester, Minn. MAIN OUTCOME MEASURES: Deltoid fat pad thickness determined by high-resolution ultrasound scanning, weight, height, and mid-deltoid arm circumference. RESULTS: We found a highly significant difference between women and men in deltoid fat pad thickness, with women having a thicker deltoid fat pad (11.7 vs 8.3 mm; P<.001). Women had a greater deltoid skin-fold thickness than men (34.7 vs 17.2 mm, P<.001) and an equal body mass index. According to the ultrasound findings, a standard 16-mm (5/8-in) needle would not have reached 5 mm into muscle in 17% (16/94) of men and 48.4% (61/126) of women in this study. CONCLUSIONS: Among healthy adults of the age range we studied, the following needle lengths appear to be appropriate for true deltoid intramuscular immunization: For men across the weight ranges we studied (59-118 kg), use of a 25-mm (1-in) needle would result in at least 5 mm of muscle penetration in all subjects. For women who weighed less than 60 kg, a 16-mm (5/8-in) needle would be sufficient to achieve muscle penetration of 5 mm. For women between 60 and 90 kg, a 25-mm (1-in) needle would be sufficient, and women greater than 90 kg would require a 38-mm (1.5-in) needle to ensure intramuscular administration.

Adult↗
PubMed1997

Measles reimmunization in children seronegative after initial immunization.

OBJECTIVE: To evaluate the success of measles reimmunization in children without measles antibody after the initial dose of measles vaccine. DESIGN AND SETTING: A prospective clinical trial in Olmsted County, Minnesota, and Northern Newfoundland and Labrador in Canada. SUBJECTS: A total of 130 healthy white, Innu, and Inuit schoolchildren. All subjects had received the post-1980 Moraten measles vaccine 4 to 11 years earlier. METHODS: Children previously identified as measles antibody seronegative or equivocal after 1 dose of measles vaccine were entered into the trial and reimmunized. Measles antibody was measured a minimum of 6 weeks later using a whole-virus IgG measles-specific enzyme-linked immunoassay (EIA). RESULTS: Of the 130 children reimmunized, 106 (81.5%) became measles antibody seropositive, but 24 children (18.5%) remained seronegative. Younger age at initial immunization (<13 months vs > or = 13 months) was significantly associated with lack of seropositive antibody levels following reimmunization (odds ratio, 3.9; 95% confidence interval, 1.5-9.7). In addition, antibody levels after reimmunization were significantly reduced with increasing time since initial immunization (P=.001). CONCLUSIONS: After 2 doses of measles vaccine, 98.2% of all subjects in this study were seropositive for measles antibody, despite the fact that almost 20% of children did not have measurable antibodies 4 to 11 years following a first dose. These findings suggest that the current public health policy recommending a 2-dose measles immunization strategy, with the second dose given at school entry, will provide high levels of immunity in the community.

Antibodies, Viral↗
PubMed1997

Polymorphisms of the TAP2 gene may influence antibody response to live measles vaccine virus.

The transporter associated with antigen processing (TAP) gene products transport peptides from the cytosol to the endoplasmic reticulum for processing by the immune system. We hypothesized that polymorphisms within the TAP genes may influence measles vaccine antigen processing and hence antibody response. TAP genotypes were determined for subjects who were measles vaccine nonresponders (n = 32) and hyper-responders (n = 28). TAP1 and TAP2 alleles were determined by PCR amplification of specific alleles (PASA). Measles vaccine nonresponders were more likely to be homozygous at TAP2 position 665 than were hyper-responders (OR = 5.0, P = 0.016). Lastly, a trend was found in the overall distribution of all TAP2 genotype frequencies between hyper-responders and nonresponders (P = 0.08). No association was found between TAP1 polymorphisms and vaccine response. These data reveal an association between TAP2 genotype and measles vaccine antibody response which may explain one mechanism behind vaccine failure.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Parameters potentially affecting interpretation of immunogenicity and efficacy data in vaccine trials: are they adequately reported?

OBJECTIVE: To describe and analyze the reporting of major factors impacting interpretation of vaccine efficacy and immunogenicity trials in recently published studies. DATA SOURCES: Selected studies (n = 83) published during a two year period in five journals most likely to contain vaccine trials. STUDY SELECTION: Studies designed as prospective efficacy or immunogenicity clinical trials in human subjects, examining an experimental or existing vaccine. DATA EXTRACTION: Primary factors (vaccine dose, number of doses, dosing interval, site of injection, vaccine route), as well as secondary factors (age, race, medical status, handling and manufacturing of the vaccines and concomitant drug use during vaccination). RESULTS: Only 24% of those studies utilizing intramuscularly administered vaccines reported needle length, 59% described the anatomic injection site, and 10% described the injection technique used. Eighty percent reported the actual vaccine dose used and the number of doses administered. Seventy percent reported the interval between doses. CONCLUSION: A high proportion of recently published vaccine trials fail to report potentially important methodological details, which may hamper the interpretation of vaccine efficacy and immunogenicity trial results.

Clinical Trials, Phase I as Topic↗
PubMed1996

Secondary failure rates of measles vaccines: a metaanalysis of published studies.

BACKGROUND: Recent measles outbreaks in highly vaccinated populations have highlighted the role of vaccine failure as a barrier to the elimination of measles. We sought to estimate the rate of secondary failure (clinical measles after vaccine-induced seroconversion) of measles vaccines using metaanalysis. METHODS: We identified 1411 studies of which 125 were relevant. From these we found 10 original studies of healthy subjects with sufficient details to calculate a pooled secondary failure rate. We performed a test for homogeneity before any pooling. RESULTS: Although significant heterogeneity prevented their pooling as a single group, the studies fell into three homogeneous groups suitable for pooling. Group A studies used killed vaccine whereas the other two groups (Groups B and C) of studies used live vaccine. These latter groups differ in that the studies in Group B share higher failure rates and are difficult to interpret with respect to the lack of verification of vaccination, immunization before 12 months of age and a non-North American study site and vaccine manufacturer. Those studies in Group C, in which US subjects were older than 12 months at vaccination and received a live US-manufactured vaccine that was documented in a medical record, had a failure rate of 0 of 2031 with a 95% confidence interval of 0.0 to 0.147%. CONCLUSIONS: Although reports of measles related to secondary failure exist, studies that permit the calculation of the rate of secondary failure demonstrate that the rate appears to be < 0.2%.

Child, Preschool↗