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Robert M Jacobson

Publications and source records attributed to Robert M Jacobson.

At least 19 recordsLinked to original sources
PubMed2007

Relationship between HLA polymorphisms and gamma interferon and interleukin-10 cytokine production in healthy individuals after rubella vaccination.

We studied the association between HLA alleles and rubella-specific gamma interferon (IFN-gamma) (Th1) and interleukin-10 (IL-10) (Th2) cytokine responses among 106 healthy children (ages, 14 to 17 years) previously immunized with two doses of rubella vaccine. Antibody titers and cytokine responses to rubella vaccination were not sex or age dependent. Several class I HLA-A (*0201, *2402, *6801) alleles were significantly associated with rubella vaccine-induced IFN-gamma secretion. Several class II HLA-DRB1 (*0101) and HLA-DQB1 (*0501) alleles were also suggestive of an association with IFN-gamma secretion. Alleles with potential associations with rubella-specific IL-10 production included HLA-A (*0201, *6801), HLA-B (*4901), and HLA-DRB1 (*1302). The class I A*0201 and A*6801 alleles were associated with both IFN-gamma and IL-10 secretion. These tentative associations need to be validated in larger studies with subjects of differing ethnicities. These results provide additional evidence that HLA genes may influence Th1- and Th2-specific cytokine response(s) following rubella immunization, which in turn can influence both cellular and humoral immune responses to rubella vaccination.

Adolescent↗
PubMed2006

Associations between measles vaccine immunity and single-nucleotide polymorphisms in cytokine and cytokine receptor genes.

BACKGROUND: Cytokines are key regulators of measles vaccine humoral and cellular immunity. Single-nucleotide polymorphisms (SNPs) that are associated with differences in cytokine levels should also influence measles vaccine-induced immunity. METHODS: We genotyped 118 measles-mumps-rubella-vaccinated subjects for SNPs from 6 cytokine genes (interleukin [IL]-2, IL-4, IL-10, IL-12A, IL-12B, and interferon [IFN]-gamma) and their receptors (IL-2RA, IL-2RB, IL-4RA, IL-10RA, IL-10RB, IL-12RB1, IL-12RB2, and IFN-gamma R). Associations of SNPs with measles-specific antibodies, lymphoproliferation, and secreted cytokines were determined using chi2 tests and analyses of covariance. RESULTS: We found significant associations (P<.05) between SNPs in the IL-2, IL-10, and IL-12RB genes and measles vaccine-induced immunity. The IVS1-100G (rs2069762) and the Ex2-34G (rs2069763) SNPs within the IL-2 gene were associated with high antibody and high lymphoproliferative responses, whereas SNPs within the IL-10 and IL-12R genes were associated with low antibody and lymphoproliferative responses to measles. SNPs within the IL-4RA and IL-12B genes varied significantly (P<.05) across immune response measures. Significant associations were also found between SNPs and secreted cytokine levels. CONCLUSIONS: Specific SNPs in the cytokine and cytokine receptor genes are significantly associated with variations in measures of the immune response to measles vaccination. These results need to be further validated in a larger cohort.

Cytokines↗
PubMed2006

Retrospective determination of ceruloplasmin in newborn screening blood spots of patients with Wilson disease.

Wilson disease is an autosomal recessive disorder of copper transport, caused by the reduced or absent function of the Wilson disease gene ATP7B on chromosome 13. The disease is characterized by reduced incorporation of copper into the ceruloplasmin protein and reduced excretion of copper into the bile. Wilson disease is effectively treated if detected early. Our study goals were to determine the feasibility of a population screening for Wilson disease using dried blood spots and to characterize the base-line ceruloplasmin concentration in newborn blood spots of patients with Wilson disease. Ceruloplasmin was analyzed in dried blood spots obtained from 353 Mayo Clinic pediatric volunteers aged from 3 months to 18 years and from 1045 anonymous newborn screening specimens using a sandwich enzyme-linked immunosorbent assay. The original newborn screening blood spots were retrieved from two patients with Wilson disease along with age-matched controls for ceruloplasmin determination. The mean (+/-SD) concentration of ceruloplasmin in the pediatric blood spots was 40.0+/-14.4 mg/dL (range 13.1 to >60 mg/dL) and newborn blood spots was 47.2+/-15.5mg/dL (range 6.5 to >60 mg/dL). Ceruloplasmin in the newborn blood spots from two Wilson disease patients were 2.6 and 2.8 mg/dL, respectively. The newborns affected with Wilson disease had significantly lower ceruloplasmin levels in blood spots than unaffected newborns. These findings support that presymptomatic screening for Wilson disease using dried blood spots could be possible, even in the newborn period.

Adenosine Triphosphatases↗
PubMed2006

Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine.

To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16-B*44 haplotype was associated with lower levels of immunoglobulin G (IgG) antibody to both measles (P=.08) and mumps (P=.03) viral antigens. The A*26-Cw*12-B*38 haplotype was associated with higher cellular immune responses to measles (P=.02) and mumps (P=.01) vaccine viruses. Subjects with the class II DRB1*03-DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles virus (P=.01) and mumps virus (P=.006). The DRB1*15/16-DQB1*06-DPB1*03 haplotype was associated with high levels of IgG antibody to measles virus (P=.09) but low levels of IgG antibody to rubella virus (P=.02), whereas DRB1*04-DQB1*03-DPB1*03 was associated with high lymphoproliferative responses to both measles (P=.01) and rubella (P=.002) vaccine viruses. A*26-Cw*12-B*38 was associated with both mumps virus-specific humoral (P=.007) and cell-mediated (P=.01) immune responses after 2 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated with both lower rubella virus IgG antibody levels (P=.02) and higher rubella virus-specific lymphoproliferation (P=.002). Better characterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level.

Adolescent↗
PubMed2006

Immune activation at effector and gene expression levels after measles vaccination in healthy individuals: a pilot study.

Cellular immunity to measles vaccination is not fully understood at the effector response and gene expression levels. We enrolled 15 healthy individuals (15-25 years old) previously vaccinated with two doses of measles-mumps-rubella-II vaccine to characterize their cellular immunity. We detected a spectrum of lymphoproliferative response (median stimulation indices of 3.4), low precursor frequencies of interferon-gamma (median 0.11%) and interleukin-4 (median 0.05%) by Elispot, and cosecretion of Th1 and Th2 cytokines after measles virus stimulation. Further, global gene expression was examined in five subjects from this cohort after vaccination with an additional dose of measles vaccine (Attenuax, Merck) to identify the genes involved in measles immunity. Linear mixed effect models were used to identify genes significantly up or downregulated in vivo between baseline and Days 7 and 14 after measles vaccination. Measles vaccination induced upregulation of a set of 80 genes, which play a role in measles immunity, signal transduction, apoptosis, cell proliferation, and metabolic pathways. Among the 34 genes that were downregulated, only interferon-alpha is known to have a direct role in measles immunity. This study suggests that measles vaccination leads to activation of multiple cellular mechanisms that can override the immunosuppressant effects of the measles virus and induce immunity.

Adolescent↗
PubMed2006

Childhood asthma and measles vaccine response.

BACKGROUND: Asthmatic patients have a TH2-predominant milieu that is associated with humoral immunity. However, little is known about whether humoral immune responses to viral antigens differ between asthmatic and nonasthmatic children. OBJECTIVE: To determine whether humoral immune response differs in asthmatic patients vs nonasthmatic patients. METHODS: Measles virus specific IgG antibody levels were determined for the Rochester Family Measles Study cohort (n = 876), a convenience sample of healthy children 5 to 12 years of age in Rochester, MN. We conducted comprehensive medical record reviews of 838 children who were eligible for this study. We determined the child's asthma status at the time of determination of antibody levels by applying predetermined criteria for asthma. Comparisons were made using the 2-sample t test or chi2 test. RESULTS: Of the 838 children, 156 (18.6%) had asthma at the time of the determination of antibody levels and were not taking systemic steroids within 14 days of specimen collection. Among those with a nonequivocal antibody reading, the seropositive response rates were similar in asthmatic patients and nonasthmatic patients (89.7% vs 90.3%, respectively; P = .83). However, the equivocal response rates were slightly higher among asthmatic patients than nonasthmatic patients (6.4% vs 4.7%, respectively). CONCLUSION: Asthmatic children seem to have similar humoral immune responses to measles vaccine as those without asthma. Although the findings reassure health care practitioners, whether this finding is generalizable to other vaccines and whether asthmatic patients with low antibody levels have normal cell-mediated immunity need to be elucidated in future studies.

Antibody Formation↗
PubMed2006

Human leukocyte antigen polymorphisms: variable humoral immune responses to viral vaccines.

Antibody formation in response to antigen stimulation remains the basis for measuring an individual's response and protection for most viral vaccines. A significant proportion of the variation in individual humoral immune response to vaccination appears to be genetic. The collection of genes found on chromosome 6 forming the human leukocyte antigen system provides one of the greatest sources of genetic variation in individuals with respect to their immunological responses. Recent research has demonstrated significant associations between vaccine response and human leukocyte antigen alleles. These associations not only explain why vaccine-induced humoral immune responses vary among individuals and between populations, but these variations may also hold the key to the development of future generations of vaccines.

Animals↗
PubMed2006

Population-based prevalence of repeated group A beta-hemolytic streptococcal pharyngitis episodes.

OBJECTIVE: To define the population-based 3-year period prevalence of repeated group A beta-hemolytic streptococcal (GABHS) pharyngitis episodes in children between 4 and 15 years of age. PATIENTS AND METHODS: Residents of Rochester, Minn (age, 4-15 years), who had 3 or more GABHS pharyngitis episodes In 1 year, at least 1 month apart, between January 1, 1996, and December 31, 1998, were Identified using the resources of the Rochester Epidemiology Project (N=536). Pharyngitis episodes (evidence of a sore throat with or without presence of fever) followed by either a positive rapid streptococcus test result or a positive plate culture test result were considered positive GABHS episodes. Age- and sex-specific prevalence rates were calculated, assuming that all residents 4 to 15 years of age in Rochester during 1996 to 1998 were at risk. RESULTS: A total of 208 children met our definition for repeated GABHS episodes between 1996 and 1998 and were included in this study. Approximately 1% of children between the ages of 4 and 15 years experienced repeated GABHS pharyngitis episodes between 1996 and 1998. This estimate increased to approximately 2% among children 4 to 6 years of age and decreased to 0.1% among children 13 to 15 years old. CONCLUSION: A relatively small proportion (1%) of children between 4 and 15 years of age experienced repeated GABHS episodes in a 3-year period; however, this proportion represents a substantial number of children who are affected at the population level. Given the increased costs associated with treating repeated GABHS episodes, further studies are necessary to determine how best to reduce episodes and treatment costs in this age group.

Adolescent↗
PubMed2005

Immunologic significance of HLA class I genes in measles virus-specific IFN-gamma and IL-4 cytokine immune responses.

The variability of immune responses modulated by human leukocyte antigen (HLA) genes and secreted cytokines is a significant factor in the development of a protective effect of measles vaccine. We studied the association between type 1 helper T cells (Th1)- and Th2-like cytokine immune responses and HLA class I alleles among 339 schoolchildren who previously received two doses of the measles vaccine. Median values for measles-specific interferon gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines were 40.7 pg/ml [interquartile range (IQR) 8.1-176.7] and 9.7 pg/ml (IQR 2.8-24.3), respectively. Class I HLA-A (*0101 and *3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-gamma secretion. HLA-A*3101 and Cw*0303 were associated with a higher median IFN-gamma response, while A*0101 and Cw*0501 were associated with lower measles-specific IFN-gamma response. We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4 secretion. Understanding the genetic factors that influence variations in cytokine secretion following measles vaccination will provide insight into the factors that influence both cell-mediated and humoral immunity to measles.

Adolescent↗
PubMed2005

Studies of equivalence in clinical vaccine research.

The development of combination vaccines as well as the improved manufacture of vaccines have resulted in the need for clinical studies seeking equivalence or non-inferiority as investigators seek to demonstrate that combination vaccines achieve the same levels of efficacy, immunogenicity, and safety as their individual counterparts. Given the nature of the statistical analysis, studies of equivalence require particular attention to sample size. The current double-significance method of Neyman-Pearson attempts to address problems with equivalence testing, but it leads to very large sample sizes and illogical results. With such large samples, one can find a clinically trivial difference that is still statistically significant. The late Professor Alvan R. Feinstein proposed a more logical approach that would call for smaller, more workable sample sizes. Understanding the issues involved in sample size calculations for such studies is important to those who design clinical vaccine studies. The implications of the calculations will have far-reaching effects on the feasibility of the study such as availability of subjects, the success with recruitment, and the overall expenses. In fact, the feasibility issues may prevent the study being undertaken at all.

Biometry↗
PubMed2005

Sample sizes and negative studies in clinical vaccine research.

Negative studies of vaccine adverse events occur with some frequency in the published literature. They serve important roles in fending off claims posed by the anti-vaccine movement and in reinforcing public health efforts to prevent diseases. Still, negative studies frequently suffer from concerns of adequate sample size. The double-significance Neyman-Pearson formula for sample size calculation that is now in vogue results in immense sample sizes that can lead to illogical interpretations. The late Professor Alvan R. Feinstein, the father of quantitative clinical epidemiology, proposed a more logical approach that would reduce the confusion and call for more moderate sample sizes. Understanding the issues involved in sample size calculations is important to those who design clinical vaccine studies. The implications of the calculations have far-reaching effects upon elements of feasibility such as the expense of the study, the ability to recruit adequate numbers, and even whether the study will be done at all.

Biometry↗
PubMed2005

Requiring influenza vaccination for health care workers: seven truths we must accept.

In this paper we outline the seven primary truths supporting the call for requiring influenza immunization of all health care workers. We view this as a serious patient safety issue, given the clear and compelling data regarding the frequency and severity of influenza infection. In addition, clear-cut safety, efficacy, economic, legal, and ethical platforms support the use of influenza vaccine. Unfortunately health care workers have demonstrated, over almost 25 years that they are unwilling to comply with voluntary influenza immunization programs utilizing a variety of education and incentive programs, at rates sufficient to protect the patients in their care. We suggest that an annual influenza immunization should be required for every health care worker with direct patient contact, unless a medical contraindication or religious objection exists, or an informed declination is signed by the health care worker. High rates of health care worker immunization will benefit patients, health care workers, their families and employers, and the communities within which they work and live.

Centers for Disease Control and Prevention, U.S.↗
PubMed2005

HLA class II alleles and measles virus-specific cytokine immune response following two doses of measles vaccine.

Measles virus-specific T cells and the production of cytokines play a critical role in the immune response following measles immunization. To understand the genetic factors that influence variation in IFN-gamma and IL-4 responses following measles immunization and to provide insight into the factors influencing both cellular and humoral immunity to measles, we assessed associations between human leukocyte antigen (HLA) class II genes and measles-specific Th1 and Th2-type cytokine responses in peripheral blood lymphocytes from 339 children previously vaccinated with two doses of measles-mumps-rubella vaccine (MMR-II). Median values for measles-specific IFN-gamma and IL-4 secretion levels were 40.73 and 9.71 pg/ml, respectively. The global tests suggested associations between measles-specific IFN-gamma response and alleles of the DRB1 and DQB1 loci (P=0.07 and P=0.02, respectively). Specifically, DRB1*0301, *0901, and *1501 alleles were significantly associated with IFN-gamma secretion. The alleles that suggested evidence of an HLA association with IL-4 secretion were DRB1*0103, *0701, and *1101. Th1 cytokine responses and DQB1 allele associations revealed that the alleles with the strongest association with IFN-gamma secretion were DQB1*0201, *0303, *0402, and *0602. Specific alleles with a suggestive association with low measles-specific Th2 cytokine responses were DQB1*0202 and *0503. In addition, DPB1*0101, *0201, and *0601 alleles provided suggestive evidence of an HLA association with measles-induced IFN-gamma response, while DPB1*0501 was associated with an IL-4 response. These data suggest that IFN-gamma and IL-4 cytokine responses to measles may be genetically restricted in part by HLA class II genes, which in turn can restrict the cellular immune response to measles vaccine.

Adolescent↗
PubMed2005

Human leukocyte antigen class II alleles and rubella-specific humoral and cell-mediated immunity following measles-mumps-rubella-II vaccination.

We examined associations between human leukocyte antigen (HLA) class II genes and both rubella-specific immunoglobulin G antibodies and lymphoproliferative responses after measles-mumps-rubella-II (MMR-II) vaccination, in a population-based sample of 346 schoolchildren. The DPB1*0301, DPB1*0401, DPB1*1301, and DPB1*1501 alleles were significantly associated with rubella vaccine-induced antibodies. Alleles suggestive of being positively associated with rubella-specific lymphoproliferative stimulation indices were DPB1*0301, DQB1*0501, DRB1*0101, and DRB1*1104. Conversely, the DPB1*0401, DPB1*1001, DPB1*1101, DQB1*0202, and DRB1*0701 alleles were negatively associated with rubella-specific lymphoproliferation. This study of HLA class II-restricted humoral and cellular immune responses to rubella provides significant insight into mechanisms of vaccine response and new vaccine development.

Adolescent↗
PubMed2005

Correlates of lymphoproliferative responses to measles, mumps, and rubella (MMR) virus vaccines following MMR-II vaccination in healthy children.

Cell-mediated immunity (CMI) to measles, mumps, and rubella viral antigens plays a critical role in providing long-term protection against these infectious diseases. We examined CMI by measuring lymphoproliferative response induced in response to stimulation with the above three antigens following two doses of measles, mumps, and rubella-II (MMR-II) vaccine in a randomly selected, population-based cohort of healthy children. We determined if a correlative and predictive intraclass relationship exists between CMI to the three components of MMR-II. We detected positive lymphoproliferative responses to measles, mumps, and rubella vaccines. Mumps vaccine used as an antigen had the highest median stimulation index followed by measles and rubella vaccines. The overall intraclass correlation value for lymphoproliferative response to measles, mumps, and rubella using Pearson's correlation was 0.61 (95% confidence interval = 0.56, 0.66). We observed a significant pairwise association to individual vaccine components between subjects in the upper and lower 10th percentile of immune response. This study demonstrates recall CMI post-MMR-II vaccination with significant intraclass correlation among the CMI responses to the three vaccine components.

Adolescent↗
PubMed2005

Extinction of the human leukocyte antigen homozygosity effect after two doses of the measles-mumps-rubella vaccine.

We have reported associations between human leukocyte antigen (HLA) homozygosity and low measles antibody levels after one dose of the measles, mumps, and rubella (MMR) vaccine. Here, we examined associations between HLA homozygosity and immune responses to MMR after two doses of vaccine. We examined associations between HLA homozygosity and measles antibody levels in a group of 178 children (cohort 1) as well as associations between homozygosity and antibody levels and lymphoproliferative responses to MMR in 346 children (cohort 2). In cohort 1, HLA homozygotes and heterozygotes had similar increases in measles antibody levels after a second dose of measles vaccine. In cohort 2, HLA homozygosity was not associated with measles immune measures after two doses of vaccine. Homozygosity at the DPB locus was associated with increased rubella antibody levels, and homozygosity at the class IA alleles was associated with lower mumps lymphoproliferative response. Homozygosity at increasing numbers of loci was also associated with lower mumps antibody levels and lymphoproliferative response. Therefore, two doses of the MMR vaccine appear to induce sufficient antibody levels and lymphoproliferative responses against measles and rubella, regardless of HLA homozygosity status. However, children who are HLA homozygous may be less protected against mumps compared with children who are heterozygous.

Antibodies↗