Mayo Vaccine Research Group

Rochester, MN, United States

Mayo Vaccine Research Group

Rochester, MN, United States
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White S.,University of Arkansas for Medical Sciences | White S.,Mayo Vaccine Research Group | Laurenzana E.,University of Arkansas for Medical Sciences | Laurenzana E.,Pennsylvania State University | And 3 more authors.
Drug Metabolism and Disposition | Year: 2011

We tested the hypothesis that differences in (+)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t 1/2λz) of METH and (+)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t 1/2λz was 37% longer than METH t 1/2λz (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t 1/2λz was significantly shorter than metabolite AMP t 1/2λz (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.

Ovsyannikova I.G.,Mayo Vaccine Research Group | Haralambieva I.H.,Mayo Vaccine Research Group | Poland G.A.,Mayo Vaccine Research Group
Human Heredity | Year: 2011

Background: The measles virus (MV) interacts with two known cellular receptors: CD46 and SLAM. The transmembrane receptor CD209 interacts with MV and augments dendritic cell infection. Methods: 764 subjects previously immunized with measles-mumps-rubella vaccine were genotyped for 66 candidate SNPs in the CD46, SLAM and CD209 genes as part of a larger study. Results: A previously detected association of the CD46 SNP rs2724384 with measles-specific antibodies was successfully replicated in this study. Increased representation of the minor allele G for an intronic CD46 SNP was associated with an allele dose-related decrease (978 vs. 522 mIU/ml, p = 0.0007) in antibody levels. This polymorphism rs2724384 also demonstrated associations with IL-6 (p = 0.02), IFN-α (p = 0.007) and TNF-α (p = 0.0007) responses. Two polymorphisms (coding rs164288 and intronic rs11265452) in the SLAM gene that were associated with measles antibody levels in our previous study were associated with IFN- γ Elispot (p = 0.04) and IL-10 responses (p = 0.0008), respectively, in this study. We found associations between haplotypes, AACGGAATGGAAAG (p = 0.009) and GGCCGAGAGGAGAG (p < 0.001), in the CD46 gene and TNF-α secretion. Conclusion: Understanding the functional and mechanistic consequences of these genetic polymorphisms on immune response variations could assist in directing new measles and potentially other viral vaccine design, and in better understanding measles immunogenetics. © 2011 S. Karger AG, Basel.

Sullivan S.J.,Mayo Vaccine Research Group | Jacobson R.M.,Mayo Vaccine Research Group | Jacobson R.M.,Mayo Medical School | Dowdle W.R.,Task Force for Global Health | And 2 more authors.
Mayo Clinic Proceedings | Year: 2010

Within 2 months of its discovery last spring, a novel influenza A (H1N1) virus, currently referred to as 2009 H1N1, caused the first influenza pandemic in decades. The virus has caused disproportionate disease among young people with early reports of virulence similar to that of seasonal influenza. This clinical review provides an update encompassing the virology, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of the 2009 H1N1 virus. Because information about this virus, its prevention, and treatment are rapidly evolving, readers are advised to seek additional information. We performed a literature search of PubMed using the following keywords: H1N1, influenza, vaccine, pregnancy, children, treatment, epidemiology, and review. Studies were selected for inclusion in this review on the basis of their relevance. Recent studies and articles were preferred. © 2010 Mayo Foundation for Medical Education and Research.

Oberg A.L.,Mayo Medical School | Oberg A.L.,Mayo Vaccine Research Group | Kennedy R.B.,Mayo Vaccine Research Group | Kennedy R.B.,Mayo Medical School | And 6 more authors.
Current Opinion in Immunology | Year: 2011

The current 'isolate, inactivate, inject' vaccine development strategy has served the field of vaccinology well, and such empirical vaccine candidate development has even led to the eradication of smallpox. However, such an approach suffers from limitations, and as an empirical approach, does not fully utilize our knowledge of immunology and genetics. A more complete understanding of the biological processes culminating in disease resistance is needed. The advent of high-dimensional assay technology and 'systems biology' along with a vaccinomics approach [1,2•] is spawning a new era in the science of vaccine development. Here we review recent developments in systems biology and strategies for applying this approach and its resulting data to expand our knowledge base and drive directed development of new vaccines. We also provide applied examples and point out new directions for the field in order to illustrate the power of systems biology. © 2011 Elsevier Ltd.

Oberg A.L.,Mayo Medical School | Oberg A.L.,Mayo Vaccine Research Group | Bot B.M.,Mayo Medical School | Bot B.M.,Seattle Genetics | And 5 more authors.
BMC Genomics | Year: 2012

Background: mRNA expression data from next generation sequencing platforms is obtained in the form of counts per gene or exon. Counts have classically been assumed to follow a Poisson distribution in which the variance is equal to the mean. The Negative Binomial distribution which allows for over-dispersion, i.e., for the variance to be greater than the mean, is commonly used to model count data as well.Results: In mRNA-Seq data from 25 subjects, we found technical variation to generally follow a Poisson distribution as has been reported previously and biological variability was over-dispersed relative to the Poisson model. The mean-variance relationship across all genes was quadratic, in keeping with a Negative Binomial (NB) distribution. Over-dispersed Poisson and NB distributional assumptions demonstrated marked improvements in goodness-of-fit (GOF) over the standard Poisson model assumptions, but with evidence of over-fitting in some genes. Modeling of experimental effects improved GOF for high variance genes but increased the over-fitting problem.Conclusions: These conclusions will guide development of analytical strategies for accurate modeling of variance structure in these data and sample size determination which in turn will aid in the identification of true biological signals that inform our understanding of biological systems. © 2012 Oberg et al.; licensee BioMed Central Ltd.

Tucker S.,University of Iowa | Poland G.A.,Mayo Vaccine Research Group
Workplace Health and Safety | Year: 2013

Health care reform calls for the nursing profession, with a focus on disease prevention and health restoration, to innovate and create new models of care that are client-centric, evidence-based, and cost-effective. To do so, nurses must develop a fundamentally different paradigm and epistemology. New care models are required that focus on issues such as evidence-based prevention. Among the prevention foci for hospitals are hospital-acquired infections, including influenza, which kills 36,000 Americans annually. One crucial step in eliminating hospital-acquired influenza is to require influenza vaccination of all health care workers. This article challenges nursing leadership to seize opportunities to lead health care initiatives and encourage courageous innovative actions that depart from old paradigms; these actions must be based on scientific evidence, reduce costs, and promote patient safety and quality care and outcomes. Copyright © 2013 American Association of Occupational Health Nurses, Inc.

Umlauf B.J.,Mayo Vaccine Research Group | Pinsky N.A.,Mayo Vaccine Research Group | Ovsyannikova I.G.,Mayo Vaccine Research Group | Poland G.A.,Mayo Vaccine Research Group
Methods in Molecular Biology | Year: 2012

High-throughput in vitro assays, which rapidly and succinctly assess the immune status of large cohorts of individuals, are essential tools for conducting population-based studies, including vaccine research. The enzyme-linked immunospot (ELISPOT) assay has emerged as a sensitive, reliable high-throughput tool to measure functional recall immunity by assessing the frequency of antigen-specific cytokine-secreting lymphocytes present in peripheral blood mononuclear cells (PBMCs). For the past 10 years, ELISPOT method has been the dominant platform and a standard for the cell-mediated immune (CMI) assays. ELISPOT assays are used extensively as a measure of CMI response to vaccines, including smallpox (vaccinia), following primary or secondary vaccination. Here, we present detailed methodology for using ELISPOT assays to detect the frequency of cytokine secreting vaccinia-specific lymphocytes including optimized protocols for growing, titrating, and inactivating vaccinia virus; isolating, cryopreserving, and thawing human PBMCs; and finally, detecting vaccinia-specific IL-10 and IFNγ secreting lymphocytes, as well as CD8 + IFNγ T cells following in vitro stimulation of PBMCs with vaccinia virus. The methods presented below, although optimized for vaccinia virus, emphasize principles that can be generally applied to create ELISPOT assays capable of assessing the immune status as well as antiviral CD8 + T cell response of individuals following primary or secondary vaccination with other licensed or novel vaccines. © 2012 Springer Science+Business Media, LLC.

Wicker S.,Goethe University Frankfurt | Marckmann G.,University of Tübingen | Poland G.A.,Mayo Vaccine Research Group | Rabenau H.F.,Goethe University Frankfurt
Infection Control and Hospital Epidemiology | Year: 2010

Despite decades of effort to encourage healthcare workers (HCWs) to be immunized, vaccination rates remain insufficient. Among German HCWs, 831 (68.4%) of 1,215 respondents supported mandatory vaccinations for HCWs in general. However, acceptance of mandatory vaccination varied significantly between physicians and nurses and also depended on the targeted disease. © 2010 by The Society for Healthcare Epidemiology of America. All rights reserved.

Tosh P.K.,Mayo Vaccine Research Group | Tosh P.K.,Mayo Medical School | Jacobson R.M.,Mayo Vaccine Research Group | Jacobson R.M.,Mayo Medical School | And 2 more authors.
Mayo Clinic Proceedings | Year: 2010

Influenza is an important contributor to population and individual morbidity and mortality. The current influenza pandemic with novel H1N1 has highlighted the need for health care professionals to better understand the processes involved in creating influenza vaccines, both for pandemic as well as for seasonal influenza. This review presents an overview of influenza-related topics to help meet this need and includes a discussion of the burden of disease, virology, epidemiology, viral surveillance, and vaccine strain selection. We then present an overview of influenza vaccine-related topics, including vaccine production, vaccine efficacy and effectiveness, influenza vaccine misperceptions, and populations that are recommended to receive vaccination. English-language articles in PubMed published between January 1, 1970, and October 7, 2009, were searched using key words human influenza, influenza vaccines, influenza A, and influenza B. © 2010 Mayo Foundation for Medical Education and Research.

Hart S.N.,Mayo Medical School | Therneau T.M.,Mayo Medical School | Zhang Y.,Mayo Medical School | Poland G.A.,Mayo Vaccine Research Group | And 2 more authors.
Journal of Computational Biology | Year: 2013

Background: Given the high technical reproducibility and orders of magnitude greater resolution than microarrays, next-generation sequencing of mRNA (RNA-Seq) is quickly becoming the de facto standard for measuring levels of gene expression in biological experiments. Two important questions must be taken into consideration when designing a particular experiment, namely, 1) how deep does one need to sequence? and, 2) how many biological replicates are necessary to observe a significant change in expression? Results: Based on the gene expression distributions from 127 RNA-Seq experiments, we find evidence that 91% ± 4% of all annotated genes are sequenced at a frequency of 0.1 times per million bases mapped, regardless of sample source. Based on this observation, and combining this information with other parameters such as biological variation and technical variation that we empirically estimate from our large datasets, we developed a model to estimate the statistical power needed to identify differentially expressed genes from RNA-Seq experiments. Conclusions: Our results provide a needed reference for ensuring RNA-Seq gene expression studies are conducted with the optimally sample size, power, and sequencing depth. We also make available both R code and an Excel worksheet for investigators to calculate for their own experiments. © Mary Ann Liebert, Inc.

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