Cellular Immunity to Category A-C Viruses in Humans

Summary

Principal Investigator: ROBERT WILLIAM FINBERG
Abstract: The UMMS Center for Translational Research on Human Immunology and Biodefense (CTRHIB) is a broad-based interdepartmental program to address, as its overall scientific theme, the role of T lymphocytes n the immunopathogenesis of and protection from category A-C viral pathogens in humans. The CTRHIB is a collaborative effort of senior and junior investigators with expertise in human immunology and research on biodefense pathogens, including translation to clinical studies. The UMMS CTRHIB includes 4 Research Projects, a Technology Development Project (TOP), and 5 Cores: Project 1 will analyze human CD4 and CDS T-cell responses to influenza virus vaccine and natural infection and define the characteristics associated with optimal vaccine-induced immune responses. Project 2 will analyze the interactions between innate and adaptive immune responses to virus infection and their effects on endothelial cell function, with a focus on the plasma leakage associated with viral hemorrhagic fevers caused by flaviviruses and hantaviruses. Project 3 will analyze heterologous immunity in flavivirus infections, defining the effects of amino acid variations on cross-reactive T-cell responses in sequential flavivirus infections. Project 4 will analyze the mechanisms underlying the selection of immunodominant epitopes from large DMA viruses, including poxviruses and herpesviruses (HHV-6). The Technology Development Project (TOP) will develop novel methods and tools for epitope discovery, characterization of virus-specific T cells, and high-throughput expansion and detection of virus-specific T cells to facilitate broad application of assays of cellular immunity. Core facilities will provide program administration/educational outreach, pilot projects funding, and centralized services for clinical studies (subject recruitment and characterization), flow cytometry, and production of MHC proteins for use by the research projects and TOP. The CTRHIB addresses important NIAID research priorities related to biodefense pathogens as well as career development for junior investigators. Organizing these activities in a single research Center facilitates cross-departmental and cross-disciplinary interactions, which will be assessed by periodic independent review. RELEVANCE: The UMMS Center for Translational Research in Human Immunology and Biodefense will address key NIAID research priorities through research on human T-cell responses to category A-C viruses (influenza, flaviviruses, hantaviruses, poxviruses, and herpesviruses) and development of new tools for analysis of human virus-specific T cells. The Center provides centralized services and coordination for the research. PROJECT 1: Human CD8+ and CD4+ T Cells Responses to Influenza Infection and Vaccination (TERAJIMA, M) PROJECT 1 The overall goal of this project is to define the human T-cell responses to influenza infection and to trivalent inactivated influenza vaccines (TIV) in younger and older adults. We hypothesize that (1) human T-cell responses in younger adults will be greater than those in older adults to vaccination and to infection, (2) human CD4+ and CD8+ T-cell responses will be lower to vaccine than to infection and (3) the TlV-induced T-cell responses will correlate with the amount of internal proteins in the individual licensed vaccines. Influenza A virus hemagglutinin (HA) is a target of protective neutralizing antibodies, which are subtypespecific and vulnerable to antigenic drift. CD4+ and CD8+ T-cell responses are thought to be more subtype cross-reactive. It is clear from studies in mouse models of influenza A virus infections that T cells can provide a second important line of defense, especially in the face of marked antigenic drift or shift due to emergence of viruses with changes in HA antibody combining sites, and there are also limited clinical studies which suggest the importance of T cells for protection, especially in a high-risk elderly population. There is, however, only a limited amount of data available on human T-cell responses to influenza infection or vaccination. Importantly there appears to be more subtype cross-reactivity among influenza A virus T cell epitopes than to the antibody epitopes on HA. At present limited data suggest that current TIVs induce low to moderate CD4+ and CD8+ T-cell responses. However, we found some individuals with high T-cell responses to TIV. Recently, we and the other group also found the amount of influenza internal proteins in the TIVs differs. Despite the recommendation and use of about 100 million vaccine doses per year in the US alone, very little is known about TIVs induction of T-cell responses and nothing is known about their contribution to vaccine associated protection. In Aim 1 we propose to analyze CD4+ and CD8+ T-cell responses to TIV vaccination in younger and older adults. In these studies, we will also compare the three US-licensed TIVs for their ability to stimulate CD4+ and CD8+ T-cell responses and for protection (in older adults). In Aim 2 we propose to characterize CD4+ and CD8+ T-cell responses to natural influenza infections in younger and older adults and compare them to the CD4+ and CD8+ T-cell responses induced by TIV. These analyses may lead to approaches towards improved influenza vaccines, which can protect against new and emerging influenza virus infections including H5N1 and other non-human strains. RELEVANCE: For efficient protection against influenza A virus infection, influenza vaccines need to induce cellular immune responses as well as neutralizing antibody responses, especially in older adults. Despite the recommendation and use of about 100 million vaccine doses per year in the US alone, very little is known about cellular immune responses induced by the vaccines and nothing is known about their contribution to protection, which we propose to study in younger and older adults to help design better influenza vaccines.
Funding Period: 2003-09-30 - 2014-03-31
more information: NIH RePORT

Top Publications

  1. pmc Circulating human rotavirus specific CD4 T cells identified with a class II tetramer express the intestinal homing receptors α4β7 and CCR9
    Miguel Parra
    Instituto de Genetica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogota, Colombia
    Virology 452:191-201. 2014
  2. pmc Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection
    Shenghua Zhou
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:11254-65. 2012
  3. pmc High activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in Puumala hantavirus induced nephropathia epidemica
    Tuula K Outinen
    Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
    J Med Virol 83:731-7. 2011
  4. pmc Complement-dependent lysis of influenza a virus-infected cells by broadly cross-reactive human monoclonal antibodies
    Masanori Terajima
    Center for Infectious Disease and Vaccine Research, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 85:13463-7. 2011
  5. pmc Pandemic influenza: implications for preparation and delivery of critical care services
    Mary Elise Manuell
    Department of Emergency Medicine, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA 01655, USA
    J Intensive Care Med 26:347-67. 2011
  6. pmc Structural and mechanistic studies of measles virus illuminate paramyxovirus entry
    Richard K Plemper
    Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America
    PLoS Pathog 7:e1002058. 2011
  7. pmc The combination of early and rapid type I IFN, IL-1α, and IL-1β production are essential mediators of RNA-like adjuvant driven CD4+ Th1 responses
    Rachel F Madera
    Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 6:e29412. 2011
  8. pmc Cross-reactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans
    Heather Friberg
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Sci Rep 1:51. 2011
  9. pmc Long term recall of memory CD8 T cells in mice to first and third generation smallpox vaccines
    Sharone Green
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Vaccine 29:1666-76. 2011
  10. pmc Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes
    Joel M O'Bryan
    Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 6:e20922. 2011

Research Grants

Detail Information

Publications76

  1. pmc Circulating human rotavirus specific CD4 T cells identified with a class II tetramer express the intestinal homing receptors α4β7 and CCR9
    Miguel Parra
    Instituto de Genetica Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogota, Colombia
    Virology 452:191-201. 2014
    ..Circulating RV-specific CD4 T cells represent a unique subset that expresses intestinal homing receptors...
  2. pmc Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection
    Shenghua Zhou
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:11254-65. 2012
    ....
  3. pmc High activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in Puumala hantavirus induced nephropathia epidemica
    Tuula K Outinen
    Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
    J Med Virol 83:731-7. 2011
    ..1,900 ml/day, P<0.001) and longer hospital stays (8 vs. 5 days, P<0.001). In conclusion, high serum IDO activity was associated with increased disease severity and renal impairment in NE...
  4. pmc Complement-dependent lysis of influenza a virus-infected cells by broadly cross-reactive human monoclonal antibodies
    Masanori Terajima
    Center for Infectious Disease and Vaccine Research, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 85:13463-7. 2011
    ....
  5. pmc Pandemic influenza: implications for preparation and delivery of critical care services
    Mary Elise Manuell
    Department of Emergency Medicine, University of Massachusetts Medical School, UMass Memorial Medical Center, Worcester, MA 01655, USA
    J Intensive Care Med 26:347-67. 2011
    ..Issues that require consideration include workforce staffing and safety, resource management, alternate sites of care surge of patients, altered standards of care, and crisis communication...
  6. pmc Structural and mechanistic studies of measles virus illuminate paramyxovirus entry
    Richard K Plemper
    Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America
    PLoS Pathog 7:e1002058. 2011
    ..Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family...
  7. pmc The combination of early and rapid type I IFN, IL-1α, and IL-1β production are essential mediators of RNA-like adjuvant driven CD4+ Th1 responses
    Rachel F Madera
    Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 6:e29412. 2011
    ..A better understanding of the critical signaling pathways by which RNA-like IRMs stimulate CD4+ Th1 responses is relevant to the rational design of improved vaccine adjuvants...
  8. pmc Cross-reactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans
    Heather Friberg
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Sci Rep 1:51. 2011
    ..These data confirm marked T cell activation and serotype-cross-reactivity during the febrile phase of dengue; however, A11-NS3(133)-specific responses did not correlate with prior antigenic exposure or current disease severity...
  9. pmc Long term recall of memory CD8 T cells in mice to first and third generation smallpox vaccines
    Sharone Green
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Vaccine 29:1666-76. 2011
    ..Our data indicate robust vaccinia-specific CD8(+) T cell recall responses to lethal secondary challenge in protected mice with no apparent effect of age on T cell pools established much earlier in life...
  10. pmc Extended interferon-alpha therapy accelerates telomere length loss in human peripheral blood T lymphocytes
    Joel M O'Bryan
    Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
    PLoS ONE 6:e20922. 2011
    ..We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes...
  11. pmc Memory CD8+ T cells from naturally acquired primary dengue virus infection are highly cross-reactive
    Heather Friberg
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunol Cell Biol 89:122-9. 2011
    ..Our data support a model whereby the order of sequential DENV infections influences the immune response to secondary heterologous DENV infection, contributing to varying disease outcomes...
  12. pmc Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults
    Jeffrey S Kennedy
    Wadsworth Center, New York State Department of Health, Albany, NY, USA
    J Infect Dis 204:1395-402. 2011
    ..LC16m8 is an attenuated cell culture-adapted Lister vaccinia smallpox vaccine missing the B5R protein and licensed for use in Japan...
  13. pmc Development of antigen-specific memory CD8+ T cells following live-attenuated chimeric West Nile virus vaccination
    Heidi L Smith
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Infect Dis 203:513-22. 2011
    ..WNV E-specific CD8(+) T cell responses were detected for up to 1 year after vaccination. The evolution of this WNV-specific T cell response is similar to that observed in established, highly immunogenic vaccines...
  14. pmc Heart and skeletal muscle are targets of dengue virus infection
    Doris Martha Salgado
    Universidad Surcolombiana and Pediatric Unit, Hospital Universitario de Neiva, Neiva, Colombia
    Pediatr Infect Dis J 29:238-42. 2010
    ..Dengue fever is one of the most significant re-emerging tropical diseases, despite our expanding knowledge of the disease, viral tropism is still not known to target heart tissues or muscle...
  15. pmc A role for the mevalonate pathway in the induction of subtype cross-reactive immunity to influenza A virus by human gammadelta T lymphocytes
    Julie M Jameson
    The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Cell Immunol 264:71-7. 2010
    ..Our results indicate that influenza virus infection induces the rapid activation and function of Vgamma9Vdelta2 T lymphocytes in the peripheral blood via a mechanism that depends on the mevalonate pathway...
  16. ncbi Altered effector functions of virus-specific and virus cross-reactive CD8+ T cells in mice immunized with related flaviviruses
    Derek W Trobaugh
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Eur J Immunol 40:1315-27. 2010
    ..Such cross-reactive T-cell responses to primary infection may affect the outcomes of sequential flavivirus infections...
  17. pmc Sequential immunization with heterologous chimeric flaviviruses induces broad-spectrum cross-reactive CD8+ T cell responses
    Rekha Singh
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Infect Dis 202:223-33. 2010
    ..These results demonstrate that the sequence of vaccination affects the expansion of cross-reactive CD8(+) T cells after heterologous chimeric flavivirus challenge...
  18. pmc Differential in vivo clearance and response to secondary heterologous infections by H2(b)-restricted dengue virus-specific CD8+ T cells
    Coreen M Beaumier
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Viral Immunol 23:477-85. 2010
    ..These results should facilitate further studies of the in vivo effects of DENV-specific T cells, including the use of genetically modified mouse strains...
  19. pmc The degree of leukocytosis and urine GATA-3 mRNA levels are risk factors for severe acute kidney injury in Puumala virus nephropathia epidemica
    Daniel H Libraty
    Department of Medicine, Medical School, University of Massachusetts, Worcester, Massachusetts, United States of America
    PLoS ONE 7:e35402. 2012
    ..We have identified novel acute illness risk factors for severe PUUV-induced AKI...
  20. pmc Human CD4+ T cell response to human herpesvirus 6
    Maria D Nastke
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:4776-92. 2012
    ..These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses...
  21. pmc A novel method to measure HLA-DM-susceptibility of peptides bound to MHC class II molecules based on peptide binding competition assay and differential IC(50) determination
    Liusong Yin
    Program in Immunology and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, United States
    J Immunol Methods 406:21-33. 2014
    ....
  22. pmc Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection
    Elizabeth Townsley
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
    Immunology 141:27-38. 2014
    ..In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation...
  23. pmc Elucidating the role of T cells in protection against and pathogenesis of dengue virus infections
    Anuja Mathew
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Future Microbiol 9:411-25. 2014
    ..The mechanisms that lead to severe disease are complex, and T-cell responses are an important component that needs to be further evaluated for the development of safe and efficacious DENV vaccines...
  24. ncbi Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection
    T K Outinen
    Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
    J Intern Med 276:387-95. 2014
    ..Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection...
  25. pmc Disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide-MHC structural features recognized by cross-reactive T cells
    Zu T Shen
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655
    J Immunol 191:5139-52. 2013
    ..These results indicate that protective heterologous immune responses can occur for disparate epitopes from unrelated viruses. ..
  26. ncbi The pathogenesis of nephropathia epidemica: new knowledge and unanswered questions
    Jukka Mustonen
    School of Medicine, University of Tampere, Tampere, Finland Department of Internal Medicine, Tampere University Hospital, Tampere, Finland Electronic address
    Antiviral Res 100:589-604. 2013
    ..Finally therapeutic aspects and directions for further research will be handled. ..
  27. pmc Cross-reactive human B cell and T cell epitopes between influenza A and B viruses
    Masanori Terajima
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Virol J 10:244. 2013
    ....
  28. pmc CD4+ T cells provide intermolecular help to generate robust antibody responses in vaccinia virus-vaccinated humans
    Liusong Yin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 190:6023-33. 2013
    ....
  29. pmc The role of MyD88 signaling in heterosubtypic influenza A virus infections
    Rachel F Madera
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Virus Res 171:216-21. 2013
    ..Our results have important implications for the generation of effective universal influenza vaccines...
  30. pmc The N-terminus of vaccinia virus host range protein C7L is essential for function
    Masanori Terajima
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Virus Genes 46:20-7. 2013
    ....
  31. pmc Dengue virus type 2 modulates endothelial barrier function through CD73
    Chinmay Patkar
    Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Am J Trop Med Hyg 88:89-94. 2013
    ..Our findings suggest that during DENV2 infection, endothelial barrier homeostasis is maintained by a balance between pro-inflammatory and pro-angiogenic cytokines, and type I interferon-dependent CD73 expression and activity...
  32. pmc A human CD4+ T cell epitope in the influenza hemagglutinin is cross-reactive to influenza A virus subtypes and to influenza B virus
    Jenny Aurielle B Babon
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Virol 86:9233-43. 2012
    ....
  33. pmc Antigen-specific T cell phenotyping microarrays using grating coupled surface plasmon resonance imaging and surface plasmon coupled emission
    James M Rice
    Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, BSP 318, Storrs, CT 06269, USA
    Biosens Bioelectron 31:264-9. 2012
    ..A dual mode GCSPRI/SPCE assay can provide a rapid, high content T cell screening/characterization tool that is useful for diagnosing disease, evaluating vaccination efficacy, or assessing responses to immunotherapeutics...
  34. pmc Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection
    Outi Laine
    Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
    Thromb Res 129:611-5. 2012
    ..The associations of the rarer alleles with variables reflecting the severity of the disease were analyzed...
  35. pmc Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice
    Smita Jaiswal
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA
    Immunology 136:334-43. 2012
    ..The BLT-NSG mice will allow assessment of human immune responses to DENV vaccines and the effects of previous immunity on subsequent DENV infections...
  36. pmc HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia virus by favoring the presentation of peptides with longer HLA-DM-mediated half-lives
    Liusong Yin
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 189:3983-94. 2012
    ....
  37. pmc Bi-specific MHC heterodimers for characterization of cross-reactive T cells
    Zu T Shen
    Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 285:33144-53. 2010
    ..A similar strategy could be used to develop reagents to analyze cross-reactive T cell responses in humans...
  38. pmc Peptide-MHC cellular microarray with innovative data analysis system for simultaneously detecting multiple CD4 T-cell responses
    Xinhui Ge
    Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
    PLoS ONE 5:e11355. 2010
    ....
  39. ncbi Efficient dengue virus (DENV) infection of human muscle satellite cells upregulates type I interferon response genes and differentially modulates MHC I expression on bystander and DENV-infected cells
    Rajas V Warke
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Gen Virol 89:1605-15. 2008
    ..The findings of this study warrant further clinical research to identify whether muscle cells are targets for DENV infection during the acute stage of the disease in vivo...
  40. ncbi Human CD8+ T cell memory generation in Puumala hantavirus infection occurs after the acute phase and is associated with boosting of EBV-specific CD8+ memory T cells
    Tamara Tuuminen
    Haartman Institute, University of Helsinki, Finland
    J Immunol 179:1988-95. 2007
    ..They also suggest that the boosting of unrelated memory T cells may be a common occurrence in human viral infections, which may have significant implications for the homeostasis of the memory T cell compartment...
  41. pmc Human CD4(+) memory T-lymphocyte responses to SARS coronavirus infection
    Daniel H Libraty
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA
    Virology 368:317-21. 2007
    ..This report expands our understanding of the specificity and duration of anti-SARS coronavirus CD4(+) T-cell immune responses...
  42. pmc Immunological memory after exposure to variola virus, monkeypox virus, and vaccinia virus
    Sumathi Sivapalasingam
    Division of Infectious Disease, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Infect Dis 195:1151-9. 2007
    ..Survivors of variola virus infection demonstrated VV-specific CD4 memory cell responses and neutralizing antibodies >40 years after infection...
  43. ncbi Antibody-dependent cellular cytotoxicity mediated by plasma obtained before secondary dengue virus infections: potential involvement in early control of viral replication
    Kamolwish Laoprasopwattana
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Infect Dis 195:1108-16. 2007
    ..In the present study, we examined the ability of plasma obtained before secondary DV infection to induce ADCC of DV-infected cells...
  44. pmc Immunopathogenesis of hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome: Do CD8+ T cells trigger capillary leakage in viral hemorrhagic fevers?
    Masanori Terajima
    Immunol Lett 113:117-20. 2007
    ..CD8+ T cells may be a potential target for therapy of some viral hemorrhagic fevers...
  45. ncbi Increased permeability of human endothelial cell line EA.hy926 induced by hantavirus-specific cytotoxic T lymphocytes
    Daisuke Hayasaka
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Virus Res 123:120-7. 2007
    ..These results suggest that cytotoxic T lymphocyte activity contribute to capillary leakage observed in patients with hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome...
  46. pmc Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses
    Daisuke Hayasaka
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Virol J 4:22. 2007
    ..In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain...
  47. ncbi Human cytotoxic CD4+ T cells recognize HLA-DR1-restricted epitopes on vaccinia virus proteins A24R and D1R conserved among poxviruses
    Shibani Mitra-Kaushik
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 179:1303-12. 2007
    ....
  48. ncbi Discovering innate immunity genes using differential display: a story of RNA helicases
    Zaida G Ramirez-Ortiz
    Center for Infectious Disease and Vaccine Research, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
    J Cell Physiol 209:636-44. 2006
    ..We show the use of Differential Display Reverse Transcription PCR methodology (DD) to analyze virus-host interactions and we present current findings in dengue virus-induced gene expression of RNA helicases...
  49. ncbi Major histocompatibility complex and T cell interactions of a universal T cell epitope from Plasmodium falciparum circumsporozoite protein
    Carlos Parra-Lopez
    Fundacion Instituto de Inmunologia de Colombia, Grupo Funcional Inmunología, Carrera 50 No 26 00, Bogota, Colombia
    J Biol Chem 281:14907-17. 2006
    ..T*-1 overlaps a region of the protein that has been described as highly polymorphic; however, the particular T*-1 residues required for anchoring to DR4 were highly conserved in Plasmodium sequences described to date...
  50. ncbi CD8 T cells, like CD4 T cells, are triggered by multivalent engagement of TCRs by MHC-peptide ligands but not by monovalent engagement
    Jennifer D Stone
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Immunol 176:1498-505. 2006
    ..Thus, the valency dependence of the response of CD8 T cells to soluble MHC-peptide reagents is the same as previously observed for CD4 T cells...
  51. ncbi Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes
    Hema S Bashyam
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 176:2817-24. 2006
    ....
  52. pmc A live, attenuated recombinant West Nile virus vaccine
    Thomas P Monath
    Acambis, 38 Sidney Street, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 103:6694-9. 2006
    ..ChimeriVax-WN02 rapidly elicits strong immune responses after a single dose, and is a promising candidate warranting further evaluation for prevention of WN disease...
  53. ncbi Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition
    Jennifer P Wang
    Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 177:7114-21. 2006
    ..A greater understanding of viral RNA-TLR7 activity relationships will promote rational approaches to interventional and vaccine strategies for important human viral pathogens...
  54. ncbi Identification of vaccinia CD8+ T-cell epitopes conserved among vaccinia and variola viruses restricted by common MHC class I molecules, HLA-A2 or HLA-B7
    Masanori Terajima
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA, 01655, USA
    Hum Immunol 67:512-20. 2006
    ..Combined with previous reports by us and others, these results show that there are some vaccinia viral proteins containing multiple epitopes restricted by different MHC molecules of humans and mice...
  55. ncbi Cell type-specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment
    Carey L Medin
    Center for Infectious Disease and Vaccine Research and Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA
    J Infect Dis 193:1070-7. 2006
    ..These results demonstrate that anti-inflammatory drugs have variable effects on IL-8 secretion in different cell types during DEN2V infection...
  56. pmc Robust intrapulmonary CD8 T cell responses and protection with an attenuated N1L deleted vaccinia virus
    Anuja Mathew
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    PLoS ONE 3:e3323. 2008
    ..Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine...
  57. ncbi Cross-reactive memory CD8(+) T cells alter the immune response to heterologous secondary dengue virus infections in mice in a sequence-specific manner
    Coreen M Beaumier
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Infect Dis 197:608-17. 2008
    ..These findings demonstrate that cross-reactive T cells from a primary infection alter the immune response during a heterologous secondary infection...
  58. pmc Assembly and biological and immunological properties of Newcastle disease virus-like particles
    Lori W McGinnes
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 84:4513-23. 2010
    ..Thus, ND VLPs are a potential NDV vaccine candidate. They may also serve as a platform to construct vaccines for other pathogens...
  59. pmc Dynamics of the CD8 T-cell response following yellow fever virus 17D immunization
    Mary Dawn T Co
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Immunology 128:e718-27. 2009
    ..The T-cell receptor Vbeta analysis revealed a diverse oligoclonal repertoire in tetramer-positive T-cell populations in two individuals. These characteristics of the YFV-specific T-cell response could contribute to vaccine effectiveness...
  60. pmc Genome-wide screening of human T-cell epitopes in influenza A virus reveals a broad spectrum of CD4(+) T-cell responses to internal proteins, hemagglutinins, and neuraminidases
    Jenny Aurielle B Babon
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Hum Immunol 70:711-21. 2009
    ..Our genome-wide screening is useful in identifying T-cell epitopes and is complementary to the approach based on the predicted binding peptides to well-studied HLA-A, -B, and -DR alleles...
  61. pmc Cross-reactive memory CD4+ T cells alter the CD8+ T-cell response to heterologous secondary dengue virus infections in mice in a sequence-specific manner
    Coreen M Beaumier
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Viral Immunol 22:215-9. 2009
    ..These data demonstrate the interaction of different components of the T-cell response in determining the immunological outcome of secondary DENV infection...
  62. pmc Dengue virus infection differentially regulates endothelial barrier function over time through type I interferon effects
    Ping Liu
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Infect Dis 200:191-201. 2009
    ..We hypothesized that direct viral effects on endothelial responsiveness to inflammatory and angiogenesis mediators can explain the DHF vascular leakage syndrome...
  63. pmc Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo
    Aniuska Becerra
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, 01655, USA
    J Med Virol 81:1403-11. 2009
    ..MCP-2 was identified in this work as a new unreported and important dengue-related protein and IP-10 was confirmed as a novel and strong pro-inflammatory marker in acute disease...
  64. pmc In vitro evidence that commercial influenza vaccines are not similar in their ability to activate human T cell responses
    Mary Dawn T Co
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Vaccine 27:319-27. 2009
    ..These data suggest that TIV vaccines are not similar in their ability to activate human T cell responses...
  65. pmc Increased activity of indoleamine 2,3-dioxygenase in serum from acutely infected dengue patients linked to gamma interferon antiviral function
    Aniuska Becerra
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Gen Virol 90:810-7. 2009
    ..Our results demonstrate that IDO plays an important role in the antiviral effect of IFN-gamma against DENV infection in vitro and suggest that it has a role in the immune response to DENV infections in vivo...
  66. pmc HLA-DR: molecular insights and vaccine design
    Lawrence J Stern
    Department of Pathology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Curr Pharm Des 15:3249-61. 2009
    ..Finally, using malaria as a model, we describe the development of a minimal subunit vaccine for the human malaria parasite Plasmodium falciparum...
  67. pmc TRAIL is a novel antiviral protein against dengue virus
    Rajas V Warke
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, S6 712, 55 Lake Ave North, Worcester, MA 01655, USA
    J Virol 82:555-64. 2008
    ..These data suggest that TRAIL plays an important role in the antiviral response to DV infection and is a candidate for antiviral interventions against DV...
  68. pmc Vaccinia peptides eluted from HLA-DR1 isolated from virus-infected cells are recognized by CD4+ T cells from a vaccinated donor
    Iwona Strug
    Department of Pathology, Proteomic and Mass Spectrometry Core Facility, Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Proteome Res 7:2703-11. 2008
    ..The peptides, derived from the I6L, D6R, and A10L viral proteins, were 15 residues in length, bound efficiently to HLA-DR1 as synthetic peptides, and were recognized by vaccinia-specific CD4 (+) T cells obtained from an immunized donor...
  69. pmc Vaccinia virus-specific CD8(+) T-cell responses target a group of epitopes without a strong immunodominance hierarchy in humans
    Masanori Terajima
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Hum Immunol 69:815-25. 2008
    ....
  70. pmc Discordance between antibody and T cell responses in recipients of trivalent inactivated influenza vaccine
    Mary Dawn T Co
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, United States
    Vaccine 26:1990-8. 2008
    ..These results show specific increases in a CD8 T cell subset and discordant T and B responses induced by the trivalent inactivated influenza vaccine...
  71. pmc Multiple glycines in TCR alpha-chains determine clonally diverse nature of human T cell memory to influenza A virus
    Yuri N Naumov
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 181:7407-19. 2008
    ....
  72. pmc Influenza A virus matrix protein 1-specific human CD8+ T-cell response induced in trivalent inactivated vaccine recipients
    Masanori Terajima
    Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    J Virol 82:9283-7. 2008
    ..These data show that TIV, which is formulated to contain surface glycoproteins to induce serotype-specific antibody responses, also contains M1, capable of inducing subtype cross-reactive CD8+ T-cell responses in some vaccinees...
  73. pmc Viral replication and paracrine effects result in distinct, functional responses of dendritic cells following infection with dengue 2 virus
    Zachary D Nightingale
    University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Leukoc Biol 84:1028-38. 2008
    ..These data demonstrate that functional maturation of DC in response to dengue infection is modified by the presence of virus through IFN-dependent and -independent mechanisms with consequences for the development of adaptive immunity...
  74. pmc Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer
    Marcia V Fournier
    Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Cancer Res 66:7095-102. 2006
    ..This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically...

Research Grants30

  1. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  2. New England Regional Center of Excellence in Biodefense and Emerging Infectious D
    Dennis L Kasper; Fiscal Year: 2013
    ..NERCE will also continue its Developmental Projects program and Career Development in Biodefense program in an effort to initiate new research efforts and to attract new investigators to this field. ..
  3. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..