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Lambert N.,Mayo Clinic Vaccine Research Group | Strebel P.,World Health Organization | Orenstein W.,Emory University | Icenogle J.,Centers for Disease Control and Prevention | And 2 more authors.
The Lancet | Year: 2015

Rubella remains an important pathogen worldwide, with roughly 100 000 cases of congenital rubella syndrome estimated to occur every year. Rubella-containing vaccine is highly effective and safe and, as a result, endemic rubella transmission has been interrupted in the Americas since 2009. Incomplete rubella vaccination programmes result in continued disease transmission, as evidenced by recent large outbreaks in Japan and elsewhere. In this Seminar, we provide present results regarding rubella control, elimination, and eradication policies, and a brief review of new laboratory diagnostics. Additionally, we provide novel information about rubella-containing vaccine immunogenetics and review the emerging evidence of interindividual variability in humoral and cell-mediated innate and adaptive immune responses to rubella-containing vaccine and their association with haplotypes and single-nucleotide polymorphisms across the human genome. © 2015 Elsevier Ltd.


Maltezou H.C.,U.S. Center for Disease Control and Prevention | Poland G.A.,Mayo Clinic Vaccine Research Group
Vaccine | Year: 2014

Health-care workers (HCWs) are at increased risk for acquisition of vaccine-preventable diseases (VPDs) and vaccination is justified in order to protect them from occupational exposure and to prevent the spread of VPDs that pose a threat to susceptible patients. Review of European vaccination policies for HCWs revealed significant differences between countries in terms of recommended vaccines, implementation frame (mandatory or recommendation), target HCW groups and health-care settings. Further, the few published studies available identified indicate significant immunity gaps among HCWs against VPDs in Europe. In order to achieve higher vaccination coverage against VPDs stronger recommendations are needed. The issue of mandatory vaccination should be considered for diseases that can be transmitted to susceptible patients (influenza, measles, mumps, rubella, hepatitis B, pertussis, varicella). The acceptance of vaccinations and of mandatory vaccinations by HCWs is a challenge and appears to be VPD-specific. © 2013 Elsevier Ltd.


Iankov I.D.,Mayo Medical School | Haralambieva I.H.,Mayo Clinic Vaccine Research Group | Galanis E.,Mayo Medical School
Vaccine | Year: 2011

Helicobacter pylori is a Gram-negative, spiral-shaped microorganism associated with acute and chronic gastritis, peptic ulcer, gastric cancer and gastric lymphomas in humans. H. pylori neutrophil-activating protein (NAP) is a major virulence factor playing a central role in pathogenesis of mucosal inflammation by immune cell attraction and Th1 cytokine response polarization. NAP is protective antigen and promising vaccine candidate against H. pylori infection. Here we present the development of measles virus (MV) vaccine strain encoding the NAP antigen. In order to facilitate the extracellular transport and detection, NAP was inserted in the human lambda immunoglobulin chain replacing a major part of the variable domain. We generated two MV vectors expressing secretory NAP forms: MV-lambda-NAP encoding the full-length constant lambda light chain domain and MV-s-NAP encoding only the N-terminus of the lambda light chain with the leader peptide. Immunization of MV permissive Ifnarko-CD46Ge transgenic mice by a single intraperitoneal injection of the NAP-expressing strains induced a robust, long-term humoral and cellular immune response against MV. Nine months post vaccination measles-neutralizing antibody titers were above the serum level considered protective for humans. Furthermore, all animals immunized with MV strains expressing the secretory NAP antigen developed strong humoral immunity against NAP, reaching titers >1:10,000 within 2-4 weeks. IFN-γ ELISpot assay confirmed that NAP-encoding MV vectors can also stimulate NAP-specific cell-mediated immunity. Our data demonstrate that MV is an excellent vector platform for expression of bacterial antigens and development of vaccines for H. pylori immunoprophylaxis in humans. © 2010 Elsevier Ltd.


Poland G.A.,Mayo Clinic Vaccine Research Group | Poland G.A.,Mayo Medical School | Jacobson R.M.,Mayo Clinic Vaccine Research Group | Jacobson R.M.,Mayo Medical School
Human Immunology | Year: 2012

In this paper we briefly review three common immunological misconceptions that feature prominently among anti-vaccinationists, and in turn, fuel patient and parental concerns, questions, and fears about vaccines. In particular, this Perspective covers a brief history of the anti-vaccine movement, and three common false immunological claims, namely, concerns over " antigenic overload," the induction of autoimmunity by vaccines, and the value of " natural immunity" versus vaccine-induced immunity. This is followed by a review of the harms that have been done by anti-vaccinationists, and a call to action. Regardless of the motivation behind such fears and anti-vaccine sentiment, common fears and concerns relevant to vaccines are evident and therefore are the subject of this Perspective. It is hoped that clinicians will find this information useful in answering concerns and misconceptions about vaccines, and in educating their patients. © 2012 American Society for Histocompatibility and Immunogenetics.


Chen W.,Mayo Medical School | Larrabee B.R.,Mayo Medical School | Ovsyannikova I.G.,Mayo Clinic Vaccine Research Group | Kennedy R.B.,Mayo Clinic Vaccine Research Group | And 3 more authors.
Genetics | Year: 2015

Two recently developed fine-mapping methods, CAVIAR and PAINTOR, demonstrate better performance over other fine-mapping methods. They also have the advantage of using only the marginal test statistics and the correlation among SNPs. Both methods leverage the fact that the marginal test statistics asymptotically follow a multivariate normal distribution and are likelihood based. However, their relationship with Bayesian fine mapping, such as BIMBAM, is not clear. In this study, we first show that CAVIAR and BIMBAM are actually approximately equivalent to each other. This leads to a fine-mapping method using marginal test statistics in the Bayesian framework, which we call CAVIAR Bayes factor (CAVIARBF). Another advantage of the Bayesian framework is that it can answer both association and fine-mapping questions. We also used simulations to compare CAVIARBF with other methods under different numbers of causal variants. The results showed that both CAVIARBF and BIMBAM have better performance than PAINTOR and other methods. Compared to BIMBAM, CAVIARBF has the advantage of using only marginal test statistics and takes about one-quarter to one-fifth of the running time. We applied different methods on two independent cohorts of the same phenotype. Results showed that CAVIARBF, BIMBAM, and PAINTOR selected the same top 3 SNPs; however, CAVIARBF and BIMBAM had better consistency in selecting the top 10 ranked SNPs between the two cohorts. Software is available at https://bitbucket.org/Wenan/caviarbf. © 2015 by the Genetics Society of America.


Poland G.A.,Mayo Clinic Vaccine Research Group | Kennedy R.B.,Mayo Clinic Vaccine Research Group | McKinney B.A.,University of Tulsa | McKinney B.A.,Laureate Institute for Brain Research | And 5 more authors.
Seminars in Immunology | Year: 2013

Vaccines, like drugs and medical procedures, are increasingly amenable to individualization or personalization, often based on novel data resulting from high throughput "omics" technologies. As a result of these technologies, 21st century vaccinology will increasingly see the abandonment of a "one size fits all" approach to vaccine dosing and delivery, as well as the abandonment of the empiric "isolate-inactivate-inject" paradigm for vaccine development. In this review, we discuss the immune response network theory and its application to the new field of vaccinomics and adversomics, and illustrate how vaccinomics can lead to new vaccine candidates, new understandings of how vaccines stimulate immune responses, new biomarkers for vaccine response, and facilitate the understanding of what genetic and other factors might be responsible for rare side effects due to vaccines. Perhaps most exciting will be the ability, at a systems biology level, to integrate increasingly complex high throughput data into descriptive and predictive equations for immune responses to vaccines. Herein, we discuss the above with a view toward the future of vaccinology. © 2013 Elsevier Ltd.


Lambert N.D.,Mayo Clinic Vaccine Research Group | Ovsyannikova I.G.,Mayo Clinic Vaccine Research Group | Pankratz V.S.,Mayo Medical School | Jacobson R.M.,Mayo Clinic Vaccine Research Group | And 2 more authors.
Expert Review of Vaccines | Year: 2012

Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults. © 2012 2012 Expert Reviews Ltd.


Ottenberg A.L.,Bioethics Research Program | Wu J.T.,Bioethics Research Program | Poland G.A.,Mayo Clinic Vaccine Research Group | Jacobson R.M.,Mayo Medical School | And 2 more authors.
American Journal of Public Health | Year: 2011

Despite improvements in clinician education, symptom awareness, and respiratory precautions, influenza vaccination rates for health care workers have remained unacceptably low for more than three decades, adversely affecting patient safety. When public health is jeopardized, and a safe, low-cost, and effective method to achieve patient safety exists, health care organizations and public health authorities have a responsibility to take action and change the status quo. Mandatory influenza vaccination for health care workers is supported not only by scientific data but also by ethical principles and legal precedent. The recent influenza pandemic provides an opportunity for policymakers to reconsider the benefits of mandating influenza vaccination for health care workers, including building public trust, enhancing patient safety, and strengthening the health care workforce.


Ovsyannikova I.G.,Mayo Clinic Vaccine Research Group
Genes and Immunity | Year: 2016

This study aimed to identify gene expression markers shared between both influenza hemagglutination inhibition (HAI) and virus-neutralization antibody (VNA) responses. We enrolled 158 older subjects who received the 2010–2011 trivalent inactivated influenza vaccine. Influenza-specific HAI and VNA titers and mRNA-sequencing were performed using blood samples obtained at Days 0, 3 and 28 post vaccination. For antibody response at Day 28 versus Day 0, several gene sets were identified as significant in predictive models for HAI (n=7) and VNA (n=35) responses. Five gene sets (comprising the genes MAZ, TTF, GSTM, RABGGTA, SMS, CA, IFNG and DOPEY) were in common for both HAI and VNA. For response at Day 28 versus Day 3, many gene sets were identified in predictive models for HAI (n=13) and VNA (n=41). Ten gene sets (comprising biologically related genes, such as MAN1B1, POLL, CEBPG, FOXP3, IL12A, TLR3, TLR7 and others) were shared between HAI and VNA. These identified gene sets demonstrated a high degree of network interactions and likelihood for functional relationships. Influenza-specific HAI and VNA responses demonstrated a remarkable degree of similarity. Although unique gene set signatures were identified for each humoral outcome, several gene sets were determined to be in common with both HAI and VNA response to influenza vaccine.Genes and Immunity advance online publication, 18 August 2016; doi:10.1038/gene.2016.34. © 2016 Macmillan Publishers Limited, part of Springer Nature.


Poland G.A.,Mayo Clinic Vaccine Research Group | Ovsyannikova I.G.,Mayo Clinic Vaccine Research Group | Kennedy R.B.,Mayo Clinic Vaccine Research Group | Lambert N.D.,Mayo Clinic Vaccine Research Group | Kirkland J.L.,Robert and Arlene Kogod Center on Aging
Current Opinion in Immunology | Year: 2014

Aging can lead to immunosenescence, which dramatically impairs the hosts' ability to develop protective immune responses to vaccine antigens. Reasons for this are not well understood. This topic's importance is reflected in the increases in morbidity and mortality due to infectious diseases among elderly persons, a population growing in size globally, and the significantly lower adaptive immune responses generated to vaccines in this population. Here, we endeavor to summarize the existing data on the genetic and immunologic correlates of immunosenescence with respect to vaccine response. We cover how the application of systems biology can advance our understanding of vaccine immunosenescence, with a view toward how such information could lead to strategies to overcome the lower immunogenicity of vaccines in the elderly. © 2014 Elsevier Ltd.

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