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Gregory A Poland

Publications and source records attributed to Gregory A Poland.

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

Importance of HLA-DQ and HLA-DP polymorphisms in cytokine responses to naturally processed HLA-DR-derived measles virus peptides.

We studied the association between class II human leukocyte antigen (HLA)-DRB1*0301 presented measles virus (MV) peptide-specific cytokine responses and DQB1 and DPB1 alleles among 313 individuals who received two doses of measles-mumps-rubella-II vaccine. The overall median IFN-gamma secretion levels (first and third quartiles) for the 19-amino acid MV phosphoprotein (MV-P)- and 14-amino acid MV nucleoprotein (MV-N)-derived peptides were 27.7 pg/ml (1.8, 109.4) and 1.9 pg/ml (-6.2, 13.0), respectively; median IL-4 secretion levels were -0.6 pg/ml (-7.1, 6.2) and 2.4 pg/ml (-3.2, 9.3), respectively. Primary statistical analyses were adjusted for previously identified DRB1 associations. A marginally significant increase in the frequency of the DQB1*0604 (p=0.02) allele was found among subjects who demonstrated detectable IL-4 levels to the MV-P peptide. Further, DPB1*0201 (p=0.02) and DPB1*1301 (p=0.09) alleles provided suggestive evidence of an association with MV-P-induced IL-4 secretion. Examination of IFN-gamma responses to MV-P and MV-N indicated that none of the individual alleles of the DQB1 and DPB1 loci were associated with peptide-induced T cell response. An increase in the frequency of DPB1*0501 (p=0.01) was found among subjects who failed to produce MV-N peptide-specific IL-4 responses. These data further confirm that HLA-DRB1 alleles are the major restriction molecules for MV-P and MV-N measles virus antigen presentation to T cells. We speculate that MV-P and MV-N peptides derived from DRB1*0301 could potentially be recognized in association with different HLA molecules, including DQB1 and DPB1; however, statistical adjustments for the effect of HLA-DR locus could potentially alter these genetic relationships. This concept provides important information supporting the use of promiscuous peptides in a peptide-based vaccine approach.

Adolescent↗
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↗
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

Accurate mass precursor ion data and tandem mass spectrometry identify a class I human leukocyte antigen A*0201-presented peptide originating from vaccinia virus.

We have used accurate mass precursor ion data generated on a hybrid linear-ion trap-Fourier transform ion cyclotron resonance mass spectrometer to augment tandem mass spectrometry (MS/MS) data generated on two different instrument types. Results from these experiments have allowed us for the first time to identify a naturally processed peptide presented by a class I human leukocyte antigen allele (HLA-A*0201) that was isolated from B cells infected by live vaccinia, the viral agent of the smallpox vaccine. The accurate mass data, in conjunction with MS/MS data, was able to identify the sequence IVIEAIHTV (aa 187-195) from the protein thymidylate kinase of vaccinia, distinguishing it from a similar sequence IVLEAIAEH: a "self-peptide" from the human protein phospholipase Cbeta3. Accurate mass data for the doubly charged species from the naturally processed and presented peptide was 497.8006, which was within 0.8 ppm of the calculated m/z of 497.8002, while being -37.3 ppm from the calculated m/z (497.7820) of the second-ranked peptide sequence IVLEAIAEH. Accurate mass data ranged from less than 0.1 to 1.2 ppm for other peptides identified in this sample. A BLAST search shows this sequence, IVIEAIHTV, is conserved in the same protein of a number of other orthopoxviruses, including the variola (smallpox) virus. Additionally, accurate mass data were able to uncover a false positive search result that was not distinguished by scoring of the match to the MS/MS data.

Amino Acid Sequence↗
PubMed2005

The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation program.

We describe the US experience with a large-scale smallpox vaccination program in the modern era and quantify the anticipated and unanticipated local and systemic side-effects of smallpox vaccination. In addition, we review unexpected issues, such as the development of myopericarditis discovered during the implementation of this program. These results constitute the largest dataset of a vaccinia vaccination program utilizing calf-lymph derived New York City Board of Health strain vaccine (Dryvax, Wyeth) since the 1970s. These results should inform current and future vaccinia vaccination programs and provide a historical rate of complications against which candidate vaccine side-effects can be compared in future clinical trials.

Animals↗
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↗