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Biomedical subjects

R M Jacobson

Publications and source records attributed to R M Jacobson.

At least 19 recordsLinked to original sources
PubMed2007

Childhood asthma and human leukocyte antigen type.

Little is known about the relationship between human leukocyte antigen (HLA) class II genes and family history of asthma or atopy in relation to the incidence of childhood asthma. The objective of the study was to determine whether specific HLA class II genes (e.g., DRB1*03) are associated with asthma and whether such association explains the influences of family history of asthma or atopy on asthma incidence. A stratified random sample of 340 children who had HLA data available from the Rochester Family Measles Study cohort (n= 876) and a convenience sample of healthy children aged 5-12 years were the participants. We conducted comprehensive medical record reviews to determine asthma status of these children. The associations between the presence of specific HLA alleles and development of asthma and the role of family history of asthma or atopy in the association were evaluated by fitting Cox models. The cumulative incidence of asthma by 12 years of age among children who carry HLA DRB1*03 was 33%, compared to 24.2% among those who did not carry this allele. Adjusting for family history of asthma or atopy, gender, low birth weight, season of birth, HLA DRB1*04, and HLA DQB1*0302, the hazards ratio for HLA DRB1*03 carriers was 1.8 (95% confidence interval: 1.1-2.9, P= 0.020). We concluded that the HLA DRB1*03 allele is associated with asthma. However, the HLA class II gene does not explain the influences of family history of asthma or atopy on development of asthma. The mechanism underlying the association between asthma and HLA genes needs to be elucidated.

Adolescent↗
PubMed2005

Selective antibody immune deficiency in a patient with Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome is a rare autosomal recessive disorder characterized by multiple congenital anomalies and various degrees of cognitive deficits. This condition results from a deficiency of 7-dehydrocholesterol reductase, a critical step in cholesterol biosynthesis. Children with Smith-Lemli-Opitz syndrome have frequent infections, particularly of the respiratory tract. Immunodeficiency, however, is not recognized as a part of this metabolic condition. Frequent infections are usually attributed to a decreased patient mobility and reduced respiratory effort secondary to muscular hypotonia and mental retardation, which are often present in affected individuals. We describe a patient with Smith-Lemli-Opitz syndrome and recurrent respiratory infections who was found to have a selective antibody deficiency. The immunological diagnosis was based on an absent immune response to Pneumovax. She also had no immunological response to hepatitis B vaccine and was unable to break down red cells with isoagglutinin B. Therapy with intravenous IgG (IVIG) was initiated. Infections were less severe, although they still occurred in a high frequency after initiation of the IVIG therapy. This finding prompts the need for a higher index of suspicion for an underlying immune deficiency in patients with Smith-Lemli-Opitz syndrome who present with recurrent and chronic infections. Early recognition and appropriate therapeutic interventions may decrease the severity of infections, prevent potentially fatal infections, and eventually improve the quality of life in these patients.

Female↗
PubMed2005

Inter-operator variation in ELISPOT analysis of measles virus-specific IFN-gamma-secreting T cells.

The ELISPOT assay is a highly sensitive technique used for the detection of individual cytokine releasing cells. We have developed an IFN-gamma ELISPOT assay utilizing unfractionated frozen peripheral blood mononuclear cells (PBMC) to quantify the frequency of measles virus (MV)-specific IFN-gamma-secreting T cells in 117 healthy children who had been previously immunized with two doses of the measles-mumps-rubella vaccine. We have also estimated the variability associated with the quantification of ELISPOT plates and compared the number of MV-specific IFN-gamma-secreting T cells for each subject as determined by two different operators of an ELISPOT reader. The median frequency of MV-specific IFN-gamma-producing memory T cells detected by this assay was 0.005 % and 0.01 % as determined by an in-house and commercial operator, respectively. Although we found a significant correlation (r = 0.83, p<0.0001) between the number of spots counted by the commercial and in-house operators of an ELISPOT reader, the median number of spots counted by the commercial operator was twice the number of spots counted by an in-house operator (p<0.001). This demonstrates the importance of using a common ELISPOT reader and operator, among other parameters, to quantify the number of spots when a large volume of plates are being scanned and analyzed.

Adolescent↗
PubMed2005

Correlations among measles virus-specific antibody, lymphoproliferation and Th1/Th2 cytokine responses following measles-mumps-rubella-II (MMR-II) vaccination.

Immunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long-term recall response. Therefore, it is important to evaluate measles-specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles-specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)-gamma and interleukin (IL)-4, in a population-based cohort of healthy children from Olmsted County, Minnesota after two doses of measles-mumps-rubella-II (MMR-II) vaccine. We detected positive measures of measles-specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL-4 and/or measles-specific antibodies and a lack of IFN-gamma production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN-gamma (r = 0.20, P = 0.0002) and IL-4 (r = 0.15, P = 0.005). Measles antibody levels were correlated with lymphoproliferation (r = 0.12, P = 0.03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long-term cellular and humoral responses after MMR-II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL-4 and IFN-gamma suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long-term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long-term follow-up is needed.

Adolescent↗
PubMed2004

The genetic basis for measles vaccine failure.

The US measles epidemics of 1989-1991 included a series of outbreaks resulting from vaccine failure. A series of studies was launched aimed at elucidating the mechanisms of this vaccine failure. A meta-analysis of the literature examining epidemics in vaccinated populations was conducted, which showed that the secondary vaccine failure rate (development of the disease despite an initial or primary vaccine success) is no more than 0.2%. The overwhelming proportion of measles vaccine failure was due to primary vaccine failure (failure to ever generate antibody from antigenic stimulation). This comparison of two geographically distinct communities revealed that 10% of children previously vaccinated against measles lacked antibody on follow-up and that these vaccine failures clustered in families. A study of monozygotic and dizygotic twins revealed a high degree of heritability of measles vaccine antibody level. Subsequent studies found associations with both class I and class II alleles in these population-based studies. In the future, detection of the specific peptides that interact with human leukocyte antigen (HLA) molecules may serve as the basis for improved vaccines and address vaccine failure that results from cold-chain problems, immaturity of the immune system, malnutrition and maternal immunity.

Antibody Formation↗
PubMed2003

Lack of association between transporter associated with antigen processing (TAP) and HLA-DM gene polymorphisms and antibody levels following measles vaccination.

The transporter associated with antigen processing (TAP) and human leukocyte antigen-DM (HLA-DM) genes are involved in the antigen-processing pathway of both HLA class I and class II-restricted antigen presentation. We hypothesized that polymorphisms within the TAP and DM genes may influence antibody levels following measles vaccination. We examined TAP and DM polymorphisms in 242 school children from Olmsted County, Minnesota, USA who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months. Based on the level of serum measles-specific immunoglobulin G (IgG) antibodies, subjects were classified as seronegatives (n = 72) or seropositives (n = 170). We determined TAP1 and TAP2 allele types by polymerase chain reaction (PCR) amplification of specific alleles (PASA) and determined DM allele type by PCR amplification followed by direct sequencing of the polymorphic sites. We analysed the data for any TAP or DM allelic association with antibody levels post measles vaccination using the chi-square test and univariate linear regression analysis. We found no trend in the overall distribution of TAP and DM genotype frequencies between seronegative and seropositive subjects, suggesting that TAP and DM polymorphism and antibody levels following measles vaccination are not directly associated. In addition, we did not find an association between TAP (TAP1, P = 0.71; TAP2, P = 0.87) or DM (DMA, P = 0.42; DMB, P = 0.71) homozygosity and seronegativity to measles vaccine in this study group. Our study suggests that TAP and DM gene polymorphisms do not influence antibody levels post measles vaccination.

ATP-Binding Cassette Transporters↗
PubMed2002

The pneumococcal conjugate vaccine.

Streptococcus pneumoniae is the most frequent cause of otitis media, sinusitis, and pneumonia in children. It is also one of the most common causes of invasive bacterial infections in children including bacteremia and meningitis. One of the current issues regarding S. pneumoniae is the emergence of pneumococcal strains resistant to penicillin and other antibiotics. Children less than two years of age suffer an increased incidence of invasive pneumococcal disease but fail to respond to the 23-valent polysaccharide vaccine because of the immaturity of the T-cell independent immune function. Covalently conjugating the polysaccharide antigen to a carrier protein improves the immune response by permitting the host to utilize a T-cell dependent immune response that is adequately mature in children less than two years of age. Immunogenicity studies of the currently licensed heptavalent conjugated polysaccharide vaccine, (Prevnar, marketed by Wyeth Lederle Vaccines) demonstrated that infants vaccinated with three doses 2 months apart at 2, 4, and 6 months of age successfully developed antibodies to all 7 serotypes; booster doses at 12-15 months demonstrated an amnestic response for each serotype. Immunogenicity studies have similarly demonstrated successful responses in children with sickle cell disease and human immunodeficiency virus infection. An efficacy trial involving nearly 38,000 subjects demonstrated the vaccine's effectiveness in healthy children against invasive pneumococcal disease as well as against pneumonia and otitis media. Currently the US Advisory Committee on Immunization Practices (ACIP) recommends that all infants and children under 24 months of age receive the vaccine. The ACIP recommends that infants receive the vaccine routinely at 2, 4 and 6 months with a fourth dose at 12 to 15 months of age. Infants may receive the first dose as early as 6 weeks of age. The vaccine is also indicated for children 24 to 59 months of age who are at high risk for pneumococcal infection. Adverse events include local reactions in the first two days following vaccination such as approximately 10% reporting erythema, 10% induration, and 20% tenderness. Fever of 38 degrees C or higher occurred in 15% to 25% of children in the first two days following vaccination. Follow-up studies should address important questions regarding the use of pneumococcal conjugate vaccine and other age groups.

Follow-Up Studies↗
PubMed2001

Identification of an association between HLA class II alleles and low antibody levels after measles immunization.

This is the first large cohort study to report a genetic association between humoral antibody level after measles vaccine and the HLA class II genes. The WHO goal to eradicate measles world-wide magnifies the importance of data relating to the influence of immunogenetics on measles vaccine-induced antibody responses. We present here the analysis of 242 individuals who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months and were genotyped for HLA class II alleles. These subjects fit into one of three categories; 72 were classified as seronegative, 93 were seropositive and 77 were serohyperpositive. HLA-DRB1*03 (odds ratio (OR), 2.22) and HLA-DPA1*0201 (OR, 1.71) were significantly associated with measles vaccine seronegativity, while additional alleles provided suggestive evidence of association with seronegativity: DQA1*0201, DQB1*0201, and DQA1*0501. The alleles DRB1*03 and DQA1*0201 remained statistically significant after accounting for the effects of other alleles. These findings are crucial in designing both measles eradication by the use of vaccine, and future vaccines to be used in genetically heterozygous populations.

Alleles↗
PubMed2001

Influenza vaccines: a review and rationale for use in developed and underdeveloped countries.

Multiple studies have demonstrated that influenza infection results in considerable morbidity and mortality, as well as other economic consequences, such as school and work absenteeism. Influenza vaccine has been shown to be both cost-effective and cost-saving. Despite this, the influenza vaccine appears to be under-utilized throughout the world, with significant variations both between countries and within countries over time. Data will be discussed that provide a rationale for the use of the influenza vaccine to protect the public health. Recommendations for the use of the influenza vaccine in various countries and guidelines for influenza vaccine use worldwide will be proposed.

Adult↗
PubMed2001

Making vaccines more acceptable--methods to prevent and minimize pain and other common adverse events associated with vaccines.

The growing abundance of highly immunogenic vaccines has arrived with a burden of pain, distress, and common adverse reactions that in turn may interfere with parental compliance and aggravate anti-vaccine sentiment. In a study of 150 children in each of 2 age-groups, we found that approximately 20% of the subjects suffered serious distress or worse. During the procedural phase, approximately 90% of the 15-to-18 month old children and 45% of the 4-to-6 year old children showed serious distress or worse. To address non-adherence with pediatric vaccine schedules, we must consider all of the possible issues that might prevent a parent from taking a child to a health care provider for vaccination. In that same study we identified useful predictors for both preparatory and procedural distress - predictors that might be used in identifying children who might benefit from preventive interventions. Vaccine providers might consider a variety of interventions. Attitude, empathy, instruction, and practice have all been shown to have a salutatory effect upon pain and anxiety with medical procedures in general and specifically with vaccinations. Distraction has also been found to be an effective method for distress and pain prevention in children. More formal methods of clinical hypnosis which combine a deep state of relaxation with focused imagery and suggestion have also been found to be effective in helping children and adolescents prepare for, cope with, and tolerate the pain and anxiety associated with medical procedures. So-called 'sugar nipples' delivering small amounts of sucrose orally at the time of a painful procedure in an infant has been not been shown to decrease vaccination pain and studies on refrigerant topical anesthetics are mixed. Studies have found a eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA) effective in providing adequate local anesthesia in children, but it suffers from problems in practical application. Studies with various injection techniques have not identified ready solutions, and although jet injection appears to provoke less anxiety and cause less immediate pain, studies also indicate a somewhat greater incidence of delayed local reactogenicity including soreness and edema. Other measures to prevent or rapidly treat other common adverse events have been shown effective and should be considered as well.

Administration, Intranasal↗
PubMed2001

Adverse events and vaccination-the lack of power and predictability of infrequent events in pre-licensure study.

The recent setback in the development of a safe and effective rotavirus vaccine illustrates an important problem regarding prelicensure testing and its ability to identify rare vaccine-related adverse effects. It is our contention that the possibility of a rare but serious vaccine adverse effect is difficult to detect in prelicensure testing. In this paper, we review the history regarding the testing and eventual studies that led to the permanent withdrawal of that vaccine. The post-licensure discovery of a serious adverse event associated with the rotavirus vaccine is not unique among vaccines, but represents a recurrent phenomenon that in fact is mathematically predictable. Prelicensure studies examine thousands of subjects and not hundreds of thousands. A sample size of 10,000 subjects may provide excellent estimates of efficacy, but cannot provide an adequate denominator to rule out rare adverse events. It lacks the power. Just as with the rotavirus vaccine, only after hundreds of thousands of doses of vaccines are distributed, will such rare events appear often enough to permit detection. For that reason, we must depend upon the modern post-licensure surveillance programs that we already have in place.

Clinical Trials as Topic↗
PubMed2001

Twin studies of immunogenicity--determining the genetic contribution to vaccine failure.

CONTEXT: Estimating the magnitude of the genetic contribution to the overall variation of antibody levels among individuals should help clarify the role of genetic association in the biological mechanism of vaccine response and failure. This, in turn, should help guide the design of improved vaccines with enhanced efficacy. OBJECTIVE: To explore the magnitude of genetic influence on antibody levels following measles, mumps and rubella vaccines. DESIGN: Cross-sectional survey study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Healthy twin-pairs. Of the 100 twin-pairs enrolled, 45 were monozygotic. INTERVENTIONS: Determinations of zygosity, vaccine status, and quantitative IgG to measles, mumps, and rubella. MAIN OUTCOME MEASURE: Heritability (ratio of genetic variance to total variance). RESULTS: The number of vaccine-doses, the age at initial immunization, and the time between immunization and sampling did not differ between monozygotic and dizygotic twin pairs. The genetic variance - the variance in antibody levels presumably due to genetic effects - was 0.49 for measles, 0.54 for mumps, and 0.13 for rubella. Heritability, the ratio of genetic variance to total variance, was 88.5% for measles, with the lower bound of a one-sided 95% confidence interval equal to 52.4%. The heritability was, for mumps, 38.8% with a lower bound of 1.60%. The heritability for rubella was 45.7% with a lower bound of 4.94%. CONCLUSION: Our data support the concept that genetic influences play a substantial role in the variation of antibody levels following immunization against measles and, to a lesser extent, mumps and rubella.

Adolescent↗
PubMed2001

Understanding those who do not understand: a brief review of the anti-vaccine movement.

Vaccines and the ability to prevent morbidity and mortality due to infectious diseases have been one of the greatest public health success stories. On a global level, it is one of the few cost-effective medical measures that result in universal benefit. Despite this, there is evidence of a growing anti-vaccine movement. In turn, this has, in some cases, resulted in major disruptions in vaccine programs, with resultant needless morbidity and mortality. Of interest are the factors that seem to contribute to the current trend of anti-vaccine sentiment. This paper will examine the current anti-vaccine movement and provide current examples. Finally, a review of suggestions for dealing with the anti-vaccine movement will be presented.

Cultural Characteristics↗
PubMed2001

The prevention of Lyme disease with vaccine.

Lyme disease is a potentially serious and debilitating infection caused by Borrelia burgdorferi that is endemic in North America, Europe, and Asia. Personal protective and environmental measures have not significantly impacted its increasing incidence. An adjuvanted recombinant vaccine (LYMErix) has been approved in the United States for the prevention of Lyme disease in adults, and has demonstrated both safety and efficacy. A clinical trial of over 10000 adults showed 76% efficacy following the third dose of a 0, 1, 12 schedule. Accelerated schedules demonstrate equivalent levels of protective antibody. Up to 100% of children 2-14 years of age achieve seroprotective levels of antibody. Booster doses induced protective levels of antibody in more than 96% of recipients when administered at months 12 and 24. Only mild or moderate, transient vaccine-associated adverse events have been reported after immunization. The vaccine is a safe and effective method of preventing Lyme disease.

Adult↗
PubMed2001

Correlations between measles, mumps, and rubella serum antibody levels in Olmsted County school children.

We examined correlations between serum antibody levels to determine whether individuals with low levels of antibody to one component of the measles, mumps, and rubella (MMR) vaccine were also likely to have low antibody levels to the other MMR vaccine components. Our results indicate that children who had a low antibody level to one component of the MMR vaccine had a modest probability of having a low antibody level to either of the other MMR vaccine components. Overall, we found small, but statistically significant, correlations between antibody levels that were largely unaffected by race, sex, age at immunization, and time since immunization. While the correlations we observed were modest, approximately 25% of our population was seronegative for at least one component of the MMR vaccine. Therefore, our results support the current policy of continuing to administer the trivalent MMR vaccine even when only a single low antibody titer is observed.

Adolescent↗
PubMed2001

High frequency of HLA-A*0103 allele in a Somali population.

We report the existence of class I HLA allele A*0103 in an ethnic group (Somali) where this allele has not been reported. This allele was discovered in a study to examine the relationship between HLA alleles and humoral antibody response to measles vaccine among recent immigrants from Somalia to Olmsted County, Minnesota. We initially used polymerase chain reaction-sequence-specific primers (PCR-SSP) to carry out HLA class I typing. Based on PCR-SSP, 55 subjects were assigned the allele HLA-A*0101. Following direct DNA sequencing of the PCR products, 37 of the 55 subjects (67.3%) that were initially assigned the A*0101 allele were found to actually be A*0103. Our data are significant because it demonstrates that many of the previously typed A*0101 individuals are actually A*0103 as the SSP or sequence-specific oligonucleotide probes method cannot distinguish between the two alleles. Lastly, this is the first identification of this allele in the homozygous state.

Alleles↗