The Experts below are selected from a list of 4122 Experts worldwide ranked by ideXlab platform
Gregory A. Poland - One of the best experts on this subject based on the ideXlab platform.
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the integration of epistasis network and functional interactions in a gwas implicates rxr pathway genes in the immune response to Smallpox Vaccine
PLOS ONE, 2016Co-Authors: Brett A Mckinney, Inna G. Ovsyannikova, Richard B. Kennedy, Ann L. Oberg, Caleb A Lareau, Gregory A. PolandAbstract:Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a Smallpox Vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of Smallpox Vaccine.
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Impaired innate, humoral, and cellular immunity despite a take in Smallpox Vaccine recipients
Vaccine, 2016Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Gregory A. Poland, Robert A Vierkant, Ann L. Oberg, Yan W. Asmann, Diane E. Grill, Robert M JacobsonAbstract:Smallpox Vaccine is highly effective, inducing protective immunity to Smallpox and diseases caused by related orthopoxviruses. Smallpox Vaccine efficacy was historically defined by the appearance of a lesion or "take" at the Vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical Vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented Vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the Smallpox Vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated Smallpox Vaccines and/or effective antiviral therapy targets against poxvirus infections.
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Cytokine production associated with Smallpox Vaccine responses
Immunotherapy, 2014Co-Authors: Whitney L. Simon, Hannah M. Salk, Inna G. Ovsyannikova, Richard B. Kennedy, Gregory A. PolandAbstract:Smallpox was eradicated 34 years ago due to the success of the Smallpox Vaccine; yet, the Vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current Smallpox Vaccines. Interindividual variations in Vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the Smallpox Vaccine compared with other Vaccines. Here, we aim to summarize the cytokine responses associated with Smallpox Vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to Smallpox vaccination.
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race and sex based differences in cytokine immune responses to Smallpox Vaccine in healthy individuals
Human Immunology, 2013Co-Authors: Iana H Haralambieva, Inna G. Ovsyannikova, Richard B. Kennedy, Beth R Larrabee, Shane V Pankratz, Gregory A. PolandAbstract:Abstract We assessed the effects of sex, race and ethnicity on Smallpox Vaccine-induced immune responses in 1071 armed forces members after primary Dryvax® Smallpox vaccination, including 790 males and 281 females; 580 Caucasians, 217 African–Americans, and 217 Hispanics. Analysis of vaccinia-specific cytokine responses revealed that Caucasians had higher total IFNγ ELISPOT responses (median 57 spot-forming units/SFUs per 200,000 cells, p = 0.01) and CD8+IFNγ ELISPOT responses (12 SFUs, p
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Genome-wide analysis of polymorphisms associated with cytokine responses in Smallpox Vaccine recipients
Human Genetics, 2012Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Robert A Vierkant, Iana H Haralambieva, V. Shane Pankratz, Gregory A. PolandAbstract:The role that genetics play in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host–pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in Smallpox Vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences Vaccine responses.
Inna G. Ovsyannikova - One of the best experts on this subject based on the ideXlab platform.
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the integration of epistasis network and functional interactions in a gwas implicates rxr pathway genes in the immune response to Smallpox Vaccine
PLOS ONE, 2016Co-Authors: Brett A Mckinney, Inna G. Ovsyannikova, Richard B. Kennedy, Ann L. Oberg, Caleb A Lareau, Gregory A. PolandAbstract:Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a Smallpox Vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of Smallpox Vaccine.
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Impaired innate, humoral, and cellular immunity despite a take in Smallpox Vaccine recipients
Vaccine, 2016Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Gregory A. Poland, Robert A Vierkant, Ann L. Oberg, Yan W. Asmann, Diane E. Grill, Robert M JacobsonAbstract:Smallpox Vaccine is highly effective, inducing protective immunity to Smallpox and diseases caused by related orthopoxviruses. Smallpox Vaccine efficacy was historically defined by the appearance of a lesion or "take" at the Vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical Vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented Vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the Smallpox Vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated Smallpox Vaccines and/or effective antiviral therapy targets against poxvirus infections.
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Cytokine production associated with Smallpox Vaccine responses
Immunotherapy, 2014Co-Authors: Whitney L. Simon, Hannah M. Salk, Inna G. Ovsyannikova, Richard B. Kennedy, Gregory A. PolandAbstract:Smallpox was eradicated 34 years ago due to the success of the Smallpox Vaccine; yet, the Vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current Smallpox Vaccines. Interindividual variations in Vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the Smallpox Vaccine compared with other Vaccines. Here, we aim to summarize the cytokine responses associated with Smallpox Vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to Smallpox vaccination.
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race and sex based differences in cytokine immune responses to Smallpox Vaccine in healthy individuals
Human Immunology, 2013Co-Authors: Iana H Haralambieva, Inna G. Ovsyannikova, Richard B. Kennedy, Beth R Larrabee, Shane V Pankratz, Gregory A. PolandAbstract:Abstract We assessed the effects of sex, race and ethnicity on Smallpox Vaccine-induced immune responses in 1071 armed forces members after primary Dryvax® Smallpox vaccination, including 790 males and 281 females; 580 Caucasians, 217 African–Americans, and 217 Hispanics. Analysis of vaccinia-specific cytokine responses revealed that Caucasians had higher total IFNγ ELISPOT responses (median 57 spot-forming units/SFUs per 200,000 cells, p = 0.01) and CD8+IFNγ ELISPOT responses (12 SFUs, p
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Genome-wide analysis of polymorphisms associated with cytokine responses in Smallpox Vaccine recipients
Human Genetics, 2012Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Robert A Vierkant, Iana H Haralambieva, V. Shane Pankratz, Gregory A. PolandAbstract:The role that genetics play in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host–pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in Smallpox Vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences Vaccine responses.
Richard B. Kennedy - One of the best experts on this subject based on the ideXlab platform.
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the integration of epistasis network and functional interactions in a gwas implicates rxr pathway genes in the immune response to Smallpox Vaccine
PLOS ONE, 2016Co-Authors: Brett A Mckinney, Inna G. Ovsyannikova, Richard B. Kennedy, Ann L. Oberg, Caleb A Lareau, Gregory A. PolandAbstract:Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a Smallpox Vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of Smallpox Vaccine.
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Impaired innate, humoral, and cellular immunity despite a take in Smallpox Vaccine recipients
Vaccine, 2016Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Gregory A. Poland, Robert A Vierkant, Ann L. Oberg, Yan W. Asmann, Diane E. Grill, Robert M JacobsonAbstract:Smallpox Vaccine is highly effective, inducing protective immunity to Smallpox and diseases caused by related orthopoxviruses. Smallpox Vaccine efficacy was historically defined by the appearance of a lesion or "take" at the Vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical Vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented Vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the Smallpox Vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated Smallpox Vaccines and/or effective antiviral therapy targets against poxvirus infections.
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Cytokine production associated with Smallpox Vaccine responses
Immunotherapy, 2014Co-Authors: Whitney L. Simon, Hannah M. Salk, Inna G. Ovsyannikova, Richard B. Kennedy, Gregory A. PolandAbstract:Smallpox was eradicated 34 years ago due to the success of the Smallpox Vaccine; yet, the Vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current Smallpox Vaccines. Interindividual variations in Vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the Smallpox Vaccine compared with other Vaccines. Here, we aim to summarize the cytokine responses associated with Smallpox Vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to Smallpox vaccination.
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race and sex based differences in cytokine immune responses to Smallpox Vaccine in healthy individuals
Human Immunology, 2013Co-Authors: Iana H Haralambieva, Inna G. Ovsyannikova, Richard B. Kennedy, Beth R Larrabee, Shane V Pankratz, Gregory A. PolandAbstract:Abstract We assessed the effects of sex, race and ethnicity on Smallpox Vaccine-induced immune responses in 1071 armed forces members after primary Dryvax® Smallpox vaccination, including 790 males and 281 females; 580 Caucasians, 217 African–Americans, and 217 Hispanics. Analysis of vaccinia-specific cytokine responses revealed that Caucasians had higher total IFNγ ELISPOT responses (median 57 spot-forming units/SFUs per 200,000 cells, p = 0.01) and CD8+IFNγ ELISPOT responses (12 SFUs, p
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Genome-wide analysis of polymorphisms associated with cytokine responses in Smallpox Vaccine recipients
Human Genetics, 2012Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Robert A Vierkant, Iana H Haralambieva, V. Shane Pankratz, Gregory A. PolandAbstract:The role that genetics play in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host–pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in Smallpox Vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences Vaccine responses.
Robert M Jacobson - One of the best experts on this subject based on the ideXlab platform.
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Impaired innate, humoral, and cellular immunity despite a take in Smallpox Vaccine recipients
Vaccine, 2016Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, Gregory A. Poland, Robert A Vierkant, Ann L. Oberg, Yan W. Asmann, Diane E. Grill, Robert M JacobsonAbstract:Smallpox Vaccine is highly effective, inducing protective immunity to Smallpox and diseases caused by related orthopoxviruses. Smallpox Vaccine efficacy was historically defined by the appearance of a lesion or "take" at the Vaccine site, which leaves behind a characteristic scar. Both the take and scar are readily recognizable and were used during the eradication effort to indicate successful vaccination and to categorize individuals as "protected." However, the development of a typical Vaccine take may not equate to the successful development of a robust, protective immune response. In this report, we examined two large (>1000) cohorts of recipients of either Dryvax(®) or ACAM2000 using a testing and replication study design and identified subgroups of individuals who had documented Vaccine takes, but who failed to develop robust neutralizing antibody titers. Examination of these individuals revealed that they had suboptimal cellular immune responses as well. Further testing indicated these low responders had a diminished innate antiviral gene expression pattern (IFNA1, CXCL10, CXCL11, OASL) upon in vitro stimulation with vaccinia virus, perhaps indicative of a dysregulated innate response. Our results suggest that poor activation of innate antiviral pathways may result in suboptimal immune responses to the Smallpox Vaccine. These genes and pathways may serve as suitable targets for adjuvants in new attenuated Smallpox Vaccines and/or effective antiviral therapy targets against poxvirus infections.
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genome wide association study of antibody response to Smallpox Vaccine
Vaccine, 2012Co-Authors: Inna G. Ovsyannikova, Richard B. Kennedy, Robert M Jacobson, Shane V Pankratz, Megan M Obyrne, Gregory A. PolandAbstract:We performed a genome-wide association study (GWAS) of antibody levels in a multi-ethnic group of 1071 healthy Smallpox Vaccine recipients. In Caucasians, the most prominent association was found with promoter SNP rs10489759 in the LOC647132 pseudogene on chromosome 1 (p = 7.77 × 10−8). In African-Americans, we identified eight genetic loci at p < 5 × 10−7. The SNP association with the lowest p-value (rs10508727, p = 1.05 × 10−10) was in the Mohawk homeobox (MKX) gene on chromosome 10. Other candidate genes included LOC388460, GPR158, ZHX2, SPIRE1, GREM2, CSMD1, and RUNX1. In Hispanics, the top six associations between genetic variants and antibody levels had p-values less than 5 × 10−7, with p = 1.78 × 10−10 for the strongest statistical association (promoter SNP rs12256830 in the PCDH15 gene). In addition, SNP rs4748153 in the immune response gene PRKCQ (protein kinase C, theta) was significantly associated with neutralizing antibody levels (p = 2.51 × 10−8). Additional SNP associations in Hispanics (p ≤ 3.40 × 10−7) were mapped to the KIF6/LOC100131899, CYP2C9, and ANKLE2/GOLGA3 genes. This study has identified candidate SNPs that may be important in regulating humoral immunity to Smallpox vaccination. Replication studies, as well as studies elucidating the functional consequences of contributing genes and polymorphisms, are underway.
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Genome-wide genetic associations with IFNγ response to Smallpox Vaccine
Human genetics, 2012Co-Authors: Richard B. Kennedy, Inna G. Ovsyannikova, V Shane Pankratz, Robert A Vierkant, Robert M Jacobson, Iana H Haralambieva, Gregory A. PolandAbstract:Smallpox is a deadly and debilitating disease that killed hundreds of millions of people in the past century alone. The use of Vaccinia virus-based Smallpox Vaccines led to the eradication of Smallpox. These Vaccines are remarkably effective, inducing the characteristic pustule or “take” at the Vaccine site in >97 % of recipients, and inducing a wide spectrum of long-lasting humoral and cellular immune responses. The mechanisms behind inter-individual Vaccine-response variability are likely to involve host genetic variation, but have not been fully characterized. We report here the first Smallpox Vaccine response genome-wide association study of over 1,000 recent recipients of Dryvax®. The data presented here focus on cellular immune responses as measured by both production of secreted IFNγ and quantitation of IFNγ secreting cells by ELISPOT assay. We identified multiple significant SNP associations in genes (RASA1, ADRA1D, TCF7L1, FAS) that are critical components of signaling pathways that directly control lymphocyte IFNγ production or cytotoxic T cell function. Similarly, we found many associations with SNPs located in genes integral to nerve cell function; findings that, given the complex interplay between the nervous and immune systems, deserve closer examination in follow-up studies.
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Genome-wide association study of antibody response to Smallpox Vaccine.
Vaccine, 2012Co-Authors: Inna G. Ovsyannikova, Richard B. Kennedy, V Shane Pankratz, Robert M Jacobson, Megan M. O'byrne, Gregory A. PolandAbstract:We performed a genome-wide association study (GWAS) of antibody levels in a multi-ethnic group of 1071 healthy Smallpox Vaccine recipients. In Caucasians, the most prominent association was found with promoter SNP rs10489759 in the LOC647132 pseudogene on chromosome 1 (p = 7.77 × 10−8). In African-Americans, we identified eight genetic loci at p
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Human Leukocyte Antigen Genotypes in the Genetic Control of Adaptive Immune Responses to Smallpox Vaccine
The Journal of infectious diseases, 2011Co-Authors: Inna G. Ovsyannikova, V Shane Pankratz, Robert A Vierkant, Robert M Jacobson, Gregory A. PolandAbstract:The impact of human leukocyte antigen (HLA) genes in controlling adaptive immune responses to Smallpox Vaccine is unknown. Smallpox (variola virus) is a devastating pathogen to humans, causing significant morbidity and mortality, and is a potential agent of bioterrorism [1]. Vaccination with vaccinia virus (VACV) protects against Smallpox and related orthopox viruses and results in long-lasting immunity [2]. Smallpox Vaccine generates humoral and cellular immunity, but the biological basis for variations in immunity is not well understood [3–5]. Genes play an important role in the host immune response to vaccination in the population. Because HLA gene polymorphisms lead to differential VACV antigen presentation, we speculated that variations in immune response to Smallpox Vaccine are influenced by polymorphisms of HLA genes. We previously demonstrated associations between HLA polymorphisms and variations in both humoral and cell-mediated immune responses to other viral Vaccines, such as measles, rubella, mumps, and influenza [6–8], and we sought to generalize our work to a different viral Vaccine model. Recent studies have demonstrated that genetic polymorphisms in several genes (MTHFR and IRF1) were associated with adverse events after Smallpox vaccination [9]. Data also suggest that certain interleukin (IL)–1, IL-4, and IL-18 gene haplotypes may predict the development of fever after Smallpox Vaccine [10]. Because HLA alleles are essential for determining the specificity of an individual's immune response, we examined the influence of HLA alleles on variability in immune responses to a licensed Smallpox Vaccine. Our present study is, to our understanding, the first study to have assessed relationships between HLA gene polymorphisms and both humoral (neutralizing antibody) and cellular (total peripheral blood mononuclear cell [PBMC] of interferon [IFN]–γ by Elispot assays, CD8α+ IFN-γ levels by Elispot assays, and secreted cytokines) immune responses in healthy individuals to primary Smallpox vaccination.
Clarissa R. Damaso - One of the best experts on this subject based on the ideXlab platform.
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Re-assembly of nineteenth-century Smallpox Vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the USA
Genome Biology, 2020Co-Authors: Annika Brinkmann, José Esparza, Andreas Nitsche, Aline R. V. Souza, Clarissa R. DamasoAbstract:AbstractAccording to a recent article published in Genome Biology, Duggan and coworkers sequenced and partially assembled five genomes of Smallpox Vaccines from the nineteenth century. No information regarding the ends of genomes was presented, and they are important to understand the evolutionary relationship of the different Smallpox Vaccine genomes during the centuries. We re-assembled the genomes, which include the largest genomes in the vaccinia lineage and one true horsepox strain. Moreover, the assemblies reveal a diverse genetic structure in the genome ends. Our data emphasize the concurrent use of horsepox and horsepox-related viruses as the Smallpox Vaccine in the nineteenth century.
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Early Smallpox Vaccine manufacturing in the United States: Introduction of the "animal Vaccine" in 1870, establishment of "Vaccine farms", and the beginnings of the Vaccine industry.
Vaccine, 2020Co-Authors: José Esparza, Seth Lederman, Andreas Nitsche, Clarissa R. DamasoAbstract:Abstract For the first 80–90 years after Jenner’s discovery of vaccination in 1796, the main strategy used to disseminate and maintain the Smallpox Vaccine was arm-to-arm vaccination, also known as Jennerian or humanized vaccination. A major advance occurred after 1860 with the development of what was known as “animal Vaccine”, which referred to growing Vaccine material from serial propagation in calves before use in humans. The use of “animal Vaccine” had several advantages over arm-to-arm vaccination: it would not transmit syphilis or other human diseases, it ensured a supply of Vaccine even in the absence of the spontaneous occurrence of cases of cowpox or horsepox, and it allowed the production of large amounts of Vaccine. The “animal Vaccine” concept was introduced in the United States in 1870 by Henry Austin Martin. Very rapidly a number of “Vaccine farms” were established in the U.S. and produced large quantities of “animal Vaccine”. These “Vaccine farms” were mostly established by medical doctors who saw an opportunity to respond to an increasing demand of Smallpox Vaccine from individuals and from health authorities, and to make a profit. The “Vaccine farms” evolved from producing only Smallpox “animal Vaccine” to manufacturing several other biologics, including diphtheria- and other antitoxins. Two major incidents of tetanus contamination happened in 1901, which led to the promulgation of the Biologics Control Act of 1902. The US Secretary of the Treasury issued licenses to produce and sell biologicals, mainly Vaccines and antitoxins. Through several mergers and acquisitions, the initial biologics licensees eventually evolved into some of the current major American industrial Vaccine companies. An important aspect that was never clarified was the source of the Vaccine stocks used to manufacture the Smallpox “animal Vaccines”. Most likely, different Smallpox Vaccine stocks were repeatedly introduced from Europe, resulting in polyclonal Vaccines that are now recognized as “variants” more appropriately than “strains”. Further, clonal analysis of modern “animal Vaccines” indicate that they are probably derived from complex recombinational events between different strains of vaccinia and horsepox. Modern sequencing technologies are now been used by us to study old Smallpox Vaccine specimens in an effort to better understand the origin and evolution of the Vaccines that were used to eradicate the Smallpox.
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equination inoculation of horsepox an early alternative to vaccination inoculation of cowpox and the potential role of horsepox virus in the origin of the Smallpox Vaccine
Vaccine, 2017Co-Authors: José Esparza, Clarissa R. Damaso, Livia Schrick, Andreas NitscheAbstract:For almost 150 years after Edward Jenner had published the “Inquiry” in 1798, it was generally assumed that the cowpox virus was the Vaccine against Smallpox. It was not until 1939 when it was shown that vaccinia, the Smallpox Vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus. A favorite candidate for a vaccinia ancestor has been the horsepox virus. Edward Jenner himself suspected that cowpox derived from horsepox and he also believed that “matter” obtained from either disease could be used as preventative of Smallpox. During the 19th century, inoculation with cowpox (vaccination) was used in Europe alongside with inoculation with horsepox (equination) to prevent Smallpox. Vaccine-manufacturing practices during the 19th century may have resulted in the use of virus mixtures, leading to different genetic modifications that resulted in present-day vaccinia strains. Horsepox, a disease previously reported only in Europe, has been disappearing on that continent since the beginning of the 20th century and now seems to have become extinct, although the virus perhaps remains circulating in an unknown reservoir. Genomic sequencing of a horsepox virus isolated in Mongolia in 1976 indicated that, while closely related to vaccinia, this horsepox virus contained additional, potentially ancestral sequences absent in vaccinia. Recent genetic analyses of extant vaccinia viruses have revealed that some strains contain ancestral horsepox virus genes or are phylogenetically related to horsepox virus. We have recently reported that a commercially produced Smallpox Vaccine, manufactured in the United States in 1902, is genetically highly similar to horsepox virus, providing a missing link in this 200-year-old mystery.
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An Early American Smallpox Vaccine Based on Horsepox.
The New England journal of medicine, 2017Co-Authors: Livia Schrick, José Esparza, Clarissa R. Damaso, Simon H. Tausch, P Wojciech Dabrowski, Andreas NitscheAbstract:Global eradication of Smallpox was driven by the development of the Smallpox Vaccine. In this report, light is shed on the origins of the vaccinia virus.
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In vitro activity of cidofovir against the emerging Cantagalo virus and the Smallpox Vaccine strain IOC.
International journal of antimicrobial agents, 2008Co-Authors: Desyree Murta Jesus, Nissin Moussatche, Clarissa R. DamasoAbstract:Abstract The antiviral effect of cidofovir was evaluated against two strains of vaccinia virus: the field strain Cantagalo virus (CTGV) and the Smallpox Vaccine IOC. The drug severely inhibited virus replication, revealing an EC 50 (drug concentration required to inhibit 50% of virus replication) of 7.68μM and 9.66μM, respectively, for CTGV and Vaccine strain IOC. Similarly, other field isolates of Cantagalo-like viruses recently collected in distinct outbreaks were equally sensitive to the drug. Pre-treatment of cells prior to infection effectively established an antiviral state, inhibiting virus replication by >90% after 24h in the absence of cidofovir. CTGV infections represent an emerging zoonosis, and outbreaks have been frequently reported in several states of Brazil. Also, the possibility of resuming the manufacture of Smallpox Vaccine supports the need to evaluate the effect of antiviral drugs on the Brazilian Vaccine strain IOC. As there is no currently approved antipoxvirus therapy, our data are extremely encouraging.