Norman Letvin

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi Heterologous prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors
    Sampa Santra
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Vaccine 27:5837-45. 2009
  2. ncbi Variability in a dominant block to SIV early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death
    Thomas F Rogers
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Virol J 7:79. 2010
  3. ncbi Local replication of simian immunodeficiency virus in the breast milk compartment of chronically-infected, lactating rhesus monkeys
    Sallie R Permar
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Retrovirology 7:7. 2010
  4. ncbi Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys
    Norman L Letvin
    Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892 3005, USA
    J Virol 78:7490-7. 2004
  5. ncbi No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys
    Norman L Letvin
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Virol 81:12368-74. 2007
  6. ncbi Contribution of T-cell receptor repertoire breadth to the dominance of epitope-specific CD8+ T-lymphocyte responses
    Edwin R Manuel
    Beth Israel Deaconess Medical Center, 41 Ave Louis Pasteur, Boston, MA 02115, USA
    J Virol 80:12032-40. 2006
  7. ncbi Progress in the development of an HIV-1 vaccine
    N L Letvin
    The author is at Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Science 280:1875-80. 1998
  8. ncbi Correlates of immune protection and the development of a human immunodeficiency virus vaccine
    Norman L Letvin
    Harvard Medical School, Boston, MA 02115, USA
    Immunity 27:366-9. 2007
  9. ncbi Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys
    Norman L Letvin
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 312:1530-3. 2006
  10. ncbi Progress and obstacles in the development of an AIDS vaccine
    Norman L Letvin
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nat Rev Immunol 6:930-9. 2006

Research Grants

  1. IMMUNOREGULATION IN AIDS
    Norman Letvin; Fiscal Year: 2007
  2. Conference HIV Vaccine Development Progress & Prospects
    Norman Letvin; Fiscal Year: 2004
  3. DNA VACCINE IMMUNITY TO HIV1 AND SIV
    Norman Letvin; Fiscal Year: 2002

Detail Information

Publications109 found, 100 shown here

  1. ncbi Heterologous prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors
    Sampa Santra
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Vaccine 27:5837-45. 2009
    ....
  2. ncbi Variability in a dominant block to SIV early reverse transcription in rhesus monkey cells predicts in vivo viral replication and time to death
    Thomas F Rogers
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Virol J 7:79. 2010
    ....
  3. ncbi Local replication of simian immunodeficiency virus in the breast milk compartment of chronically-infected, lactating rhesus monkeys
    Sallie R Permar
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Retrovirology 7:7. 2010
    ..These findings suggest that a substantial fraction of milk viruses are produced by locally-infected cells, but are shaped by cellular immune pressures similar to that in the blood...
  4. ncbi Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys
    Norman L Letvin
    Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892 3005, USA
    J Virol 78:7490-7. 2004
    ....
  5. ncbi No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys
    Norman L Letvin
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Virol 81:12368-74. 2007
    ..Rather, innate immune mechanisms or an intact epithelial barrier may be responsible for protection against mucosal infection in this population of monkeys...
  6. ncbi Contribution of T-cell receptor repertoire breadth to the dominance of epitope-specific CD8+ T-lymphocyte responses
    Edwin R Manuel
    Beth Israel Deaconess Medical Center, 41 Ave Louis Pasteur, Boston, MA 02115, USA
    J Virol 80:12032-40. 2006
    ....
  7. ncbi Progress in the development of an HIV-1 vaccine
    N L Letvin
    The author is at Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Science 280:1875-80. 1998
    ..Our growing understanding of the biology of HIV-1 and immune responses to this virus will continue to suggest improved vaccination approaches for exploration...
  8. ncbi Correlates of immune protection and the development of a human immunodeficiency virus vaccine
    Norman L Letvin
    Harvard Medical School, Boston, MA 02115, USA
    Immunity 27:366-9. 2007
    ....
  9. ncbi Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys
    Norman L Letvin
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 312:1530-3. 2006
    ..These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans...
  10. ncbi Progress and obstacles in the development of an AIDS vaccine
    Norman L Letvin
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nat Rev Immunol 6:930-9. 2006
    ..This is therefore an ideal time to review our current understanding of HIV-1 and its control by the immune system, as well as the remaining problems that must be solved to facilitate the development of an effective vaccine against AIDS...
  11. ncbi Progress toward an HIV vaccine
    Norman L Letvin
    Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Annu Rev Med 56:213-23. 2005
    ..These vaccine strategies, including plasmid DNA and live recombinant vectors, are currently being evaluated in human clinical trials...
  12. ncbi Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates
    Sampa Santra
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P. O. Box 15732, Boston, MA 02215, USA
    J Virol 79:6516-22. 2005
    ..Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection...
  13. ncbi Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys
    Sampa Santra
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 168:1847-53. 2002
    ..The later emerging CTL response specific for the subdominant epitope may contribute to the control of viral replication in the setting of chronic infection...
  14. ncbi Evaluation of combination DNA/replication-competent Ad-SIV recombinant immunization regimens in rhesus macaques
    Nina Malkevitch
    Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892, USA
    AIDS Res Hum Retroviruses 20:235-44. 2004
    ..We conclude that two sequential immunizations with the same replication-competent Ad5hr-SIV recombinant is as effective as priming with one or two recombinant DNA vaccines followed by a single Ad5hrSIV recombinant immunization...
  15. ncbi Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes
    Dan H Barouch
    Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nature 415:335-9. 2002
    ..These data indicate that viral escape from CTL recognition may be a major limitation of the CTL-based AIDS vaccines that are likely to be administered to large human populations over the next several years...
  16. ncbi Dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced IL-2 expression by central memory CD4+ T lymphocytes
    Yue Sun
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 174:4753-60. 2005
    ..Persisting clinical protection in vaccinated and challenged monkeys is thus correlated with a preserved capacity of the peripheral blood central memory CD4+ T cells to express this important immunomodulatory cytokine...
  17. ncbi Vaccine protection against functional CTL abnormalities in simian human immunodeficiency virus-infected rhesus monkeys
    Paul F McKay
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    J Immunol 168:332-7. 2002
    ..Moreover, an AIDS vaccine that confers protection against clinical disease evolution in this experimental model also preserves the functional capacity of these CTL to produce both IL-2 and TNF-alpha...
  18. ncbi Cellular immunity elicited by human immunodeficiency virus type 1/ simian immunodeficiency virus DNA vaccination does not augment the sterile protection afforded by passive infusion of neutralizing antibodies
    John R Mascola
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Virol 77:10348-56. 2003
    ..These data suggest that although effector T cells can limit viral replication, they are not able to assist humoral immunity to prevent the establishment of initial infection...
  19. ncbi Recombinant vector-induced HIV/SIV-specific CD4+ T lymphocyte responses in rhesus monkeys
    Yue Sun
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Virology 406:48-55. 2010
    ..These results demonstrate that vaccine strategies that include recombinant MVA or recombinant Ad5 vectors can elicit robust CD4(+) T cell responses...
  20. ncbi Low-dose mucosal simian immunodeficiency virus infection restricts early replication kinetics and transmitted virus variants in rhesus monkeys
    Jinyan Liu
    Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Virol 84:10406-12. 2010
    ..These findings have implications for the design and interpretation of HIV-1 vaccine efficacy studies...
  21. ncbi T-cell dynamics during acute SIV infection
    Joseph J Mattapallil
    Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20895, USA
    AIDS 18:13-23. 2004
    ..Changes in homeostasis and associated immunopathogenesis can no longer be accurately described simply by measuring naive and memory T-cell subsets...
  22. ncbi The impact of a boosting immunogen on the differentiation of secondary memory CD8+ T cells
    Avi Hai Hovav
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA
    J Virol 81:12793-802. 2007
    ..These data therefore suggest that the phenotype of secondary CD8+ T cells is determined predominantly by the boosting immunogen whereas the cytokine profile of these cells is shaped by both the priming and boosting immunogens...
  23. ncbi Systemic and mucosal T-lymphocyte activation induced by recombinant adenovirus vaccines in rhesus monkeys
    Yue Sun
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Virol 83:10596-604. 2009
    ..These findings indicate that the administration of a vaccine vector such as Ad5 can induce a global activation of T cells...
  24. ncbi Neutralizing antibodies as a potential secondary protective mechanism during chronic SHIV infection in CD8+ T-cell-depleted macaques
    Robert A Rasmussen
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
    AIDS 16:829-38. 2002
    ..In addition, the results suggest that in the absence of CD8+ T cells, nAb may act as an effective second line of defense by limiting both the spread of infectious virus to new target cells and CD4+ T-cell loss...
  25. ncbi Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys
    Lauren E Grandpre
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
    Vaccine 27:1549-56. 2009
    ..Together, these studies suggest that a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates robust and durable antibody-mediated immunity comparable to that elicited by replication-competent VV...
  26. ncbi Potent CD4+ T cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing gp120 and GM-CSF
    Dan H Barouch
    Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Immunol 168:562-8. 2002
    ..These results demonstrate that bicistronic DNA vaccines containing GM-CSF elicit remarkably potent CD4(+) T cell responses and suggest that optimal Th cell priming requires the precise temporal and spatial codelivery of Ag and GM-CSF...
  27. ncbi Magnitude and quality of vaccine-elicited T-cell responses in the control of immunodeficiency virus replication in rhesus monkeys
    Yue Sun
    Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 82:8812-9. 2008
    ..These observations highlight the contributions of both the quality and the magnitude of vaccine-elicited cellular immune responses in the control of immunodeficiency virus replication...
  28. ncbi Immune failure in the absence of profound CD4+ T-lymphocyte depletion in simian immunodeficiency virus-infected rapid progressor macaques
    Vanessa M Hirsch
    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland 20852, USA
    J Virol 78:275-84. 2004
    ..The lack of CD4 depletion and loss of humoral and cellular immune responses suggest that their immune defect may be due to an early loss in T helper function...
  29. ncbi Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease
    Roland C Zahn
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    Blood 115:3070-8. 2010
    ..Thus, adaptive immune responses in natural hosts appear to be less critical for viral containment than in HIV infection...
  30. ncbi Role of genes that modulate host immune responses in the immunogenicity and pathogenicity of vaccinia virus
    Shawn S Jackson
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Research East -RE 113, 330 Brookline Ave, Boston, Massachusetts 02215, USA
    J Virol 79:6554-9. 2005
    ..Improved vaccinia virus vectors can be generated by deleting additional genes to achieve a more significant viral attenuation...
  31. ncbi Rapid memory CD8+ T-lymphocyte induction through priming with recombinant Mycobacterium smegmatis
    Avi Hai Hovav
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA
    J Virol 81:74-83. 2007
    ....
  32. ncbi Generation of CD8+ T-cell responses by a recombinant nonpathogenic Mycobacterium smegmatis vaccine vector expressing human immunodeficiency virus type 1 Env
    Mark J Cayabyab
    Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02130, USA
    J Virol 80:1645-52. 2006
    ..Importantly, preexisting immunity to Mycobacterium bovis BCG had only a marginal effect on the immunogenicity of recombinant M. smegmatis. This mycobacterium may therefore be a useful vaccine vector...
  33. ncbi Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys
    Michael S Seaman
    Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave. RE-113, Boston, MA 02215, USA
    J Virol 79:4580-8. 2005
    ..These data indicate that specific MHC class I alleles can confer protection in the setting of a pathogenic SHIV infection by their ability to elicit memory CTL following vaccination...
  34. ncbi Multiclade human immunodeficiency virus type 1 envelope immunogens elicit broad cellular and humoral immunity in rhesus monkeys
    Michael S Seaman
    Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave./RE-113, Boston, MA 02215, USA
    J Virol 79:2956-63. 2005
    ..This study demonstrates that it is possible to generate protective immune responses by vaccination with genetically diverse isolates of HIV-1...
  35. ncbi Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses
    Sampa Santra
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:11088-93. 2004
    ..This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine...
  36. ncbi Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys
    Sampa Santra
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 16:324-8. 2010
    ....
  37. ncbi Memory CD4+ T-lymphocyte loss and dysfunction during primary simian immunodeficiency virus infection
    Yue Sun
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Virol 81:8009-15. 2007
    ....
  38. ncbi T-cell vaccination reduces simian immunodeficiency virus levels in semen
    James B Whitney
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Virol 83:10840-3. 2009
    ..A vaccine that decreases the quantity of HIV-1 in the semen of males during primary infection might decrease HIV-1 transmission in human populations and therefore affect the spread of AIDS...
  39. ncbi Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses
    Mark J Cayabyab
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 83:5505-13. 2009
    ..The vaccine-elicited cellular responses were predominantly polyfunctional CD8(+) T cells. These findings support the further exploration of mycobacteria as priming vaccine vectors...
  40. ncbi Prior vaccination increases the epitopic breadth of the cytotoxic T-lymphocyte response that evolves in rhesus monkeys following a simian-human immunodeficiency virus infection
    Sampa Santra
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 76:6376-81. 2002
    ..These data indicate that prior vaccination can increase the breadth of the CTL response that evolves after an AIDS virus infection...
  41. ncbi Comparative evaluation of three different intramuscular delivery methods for DNA immunization in a nonhuman primate animal model
    Srinivas S Rao
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Vaccine 24:367-73. 2006
    ....
  42. ncbi Monitoring HIV vaccine trial participants for primary infection: studies in the SIV/macaque model
    James B Whitney
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    AIDS 23:1453-60. 2009
    ..We have utilized the SIV/rhesus monkey model to evaluate whether samples more easily obtained than peripheral blood might be used for intensive monitoring of vaccine trial participants...
  43. ncbi Partial protection of Simian immunodeficiency virus (SIV)-infected rhesus monkeys against superinfection with a heterologous SIV isolate
    Wendy W Yeh
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, CLS 1043, 3 Blackfan Circle, Boston, MA 02115, USA
    J Virol 83:2686-96. 2009
    ....
  44. ncbi Germinal center function in the spleen during simian HIV infection in rhesus monkeys
    David H Margolin
    Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    J Immunol 177:1108-19. 2006
    ....
  45. ncbi Potent simian immunodeficiency virus-specific cellular immune responses in the breast milk of simian immunodeficiency virus-infected, lactating rhesus monkeys
    Sallie R Permar
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 181:3643-50. 2008
    ..This robust viral-specific cellular immune response in breast milk may contribute to control of breast milk virus replication...
  46. ncbi Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins
    John R Mascola
    Vaccine Research Center, NIAID, NIH, 40 Convent Dr, Bethesda, MD 20892, USA
    J Virol 79:771-9. 2005
    ....
  47. ncbi Preservation of functional virus-specific memory CD8+ T lymphocytes in vaccinated, simian human immunodeficiency virus-infected rhesus monkeys
    Paula M Acierno
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, USA
    J Immunol 176:5338-45. 2006
    ....
  48. ncbi Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys
    Piya Sircar
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 185:2191-9. 2010
    ....
  49. ncbi Heterologous prime/boost immunization of rhesus monkeys by using diverse poxvirus vectors
    Sampa Santra
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Virol 81:8563-70. 2007
    ..This study supports further exploration of combining recombinant vectors of the same family in prime/boost immunization strategies to optimize vaccine-elicited cellular immune responses...
  50. ncbi Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge
    Yue Sun
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, Boston, MA 02215, USA
    J Virol 80:10950-6. 2006
    ..These findings underscore the contribution of virus-specific central memory T lymphocytes to controlling clinical progression in vaccinated individuals following a primate immunodeficiency virus infection...
  51. ncbi Autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus SIVmac251 infection of rhesus monkeys
    Wendy W Yeh
    Division of Viral Pathogenesis, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    J Virol 84:6018-32. 2010
    ..They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies...
  52. ncbi Use of molecular beacons for rapid, real-time, quantitative monitoring of cytotoxic T-lymphocyte epitope mutations in simian immunodeficiency virus
    Fred W Peyerl
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Clin Microbiol 43:4773-9. 2005
    ..This real-time PCR technique for evaluating CTL epitope mutations may prove to be a useful tool for monitoring the genetic drift of human immunodeficiency virus and SIV in infected individuals...
  53. ncbi Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination
    Jamal Baig
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 76:11484-90. 2002
    ..These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses...
  54. ncbi Global dysfunction of CD4 T-lymphocyte cytokine expression in simian-human immunodeficiency virus/SIV-infected monkeys is prevented by vaccination
    Paul F McKay
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 77:4695-702. 2003
    ....
  55. ncbi Subsets of memory cytotoxic T lymphocytes elicited by vaccination influence the efficiency of secondary expansion in vivo
    Michael S Seaman
    Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 78:206-15. 2004
    ..These observations suggest that CTL-based vaccines should elicit central memory rather than effector memory T cells and illustrate the importance of monitoring the phenotype and functionality of vaccine-induced, antigen-specific CTL...
  56. ncbi Induction of an AIDS virus-related tuberculosis-like disease in macaques: a model of simian immunodeficiency virus- mycobacterium coinfection
    Yun Shen
    Tuberculosis Research Unit, Beth Israel Deaconess Center. Harvard Medical School, Boston, Massachusetts 02215, USA
    Infect Immun 70:869-77. 2002
    ..These results provide in vivo evidence that coinfection of AIDS virus-infected individuals with an avirulent mycobacterium can lead to development of a tuberculosis-like disease...
  57. ncbi A simian immunodeficiency virus nef peptide is a dominant cytotoxic T lymphocyte epitope in Indian-origin rhesus monkeys expressing the common MHC class I allele mamu-A*02
    Michael H Newberg
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Virology 301:365-73. 2002
    ..Knowledge of this dominant CTL epitope should prove valuable in the evaluation of HIV vaccine strategies using this animal model...
  58. ncbi Limited contribution of humoral immunity to the clearance of measles viremia in rhesus monkeys
    Sallie R Permar
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Infect Dis 190:998-1005. 2004
    ....
  59. ncbi Plasmid DNA vaccine-elicited cellular immune responses limit in vivo vaccine antigen expression through Fas-mediated apoptosis
    John R Greenland
    Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, 41 Avenue Louis Pasteur, Boston, MA 02215, USA
    J Immunol 178:5652-8. 2007
    ..These findings argue that it may not be possible to maintain persistent, high-level production of vaccine Ag in vivo to drive persistent immune responses as long as vaccine Ag production can be limited by host immune responses...
  60. ncbi Clonal focusing of epitope-specific CD8+ T lymphocytes in rhesus monkeys following vaccination and simian-human immunodeficiency virus challenge
    Pritha Sen
    Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, 330 Brookline Ave, Boston, MA 02215, USA
    J Virol 82:805-16. 2008
    ..Circumventing this restricted CD8(+) T-lymphocyte clonal diversity may present a significant challenge in the development of an effective HIV vaccine strategy...
  61. ncbi A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of progressive multifocal leukoencephalopathy
    Renaud A Du Pasquier
    Division of ViralPathogenesis Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Brain 127:1970-8. 2004
    ..Fluctuations of JCV-specific CTL in the blood are associated with variation in disease manifestations. These results indicate that JCV-specific CTL are associated with the control of PML...
  62. ncbi Dominant CD8+ T-lymphocyte responses suppress expansion of vaccine-elicited subdominant T lymphocytes in rhesus monkeys challenged with pathogenic simian-human immunodeficiency virus
    Edwin R Manuel
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, E CLS Room 1043, Boston, Massachusetts 02215, USA
    J Virol 83:10028-35. 2009
    ..These findings suggest that immunodomination exerted by dominant responses during SHIV infection may diminish the breadth of recall responses primed during vaccination...
  63. ncbi Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge
    Joseph J Mattapallil
    Vaccine Research Center, National Institute of Allergy and Infectious Disease (NIAID, National Institutes of Health (NIH, Bethesda, MD 20892, USA
    J Exp Med 203:1533-41. 2006
    ....
  64. ncbi Recruitment and expansion of dendritic cells in vivo potentiate the immunogenicity of plasmid DNA vaccines
    Shawn M Sumida
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 114:1334-42. 2004
    ..Synergistic recruitment and expansion of DCs in vivo may prove a practical strategy for overcoming this limitation and potentiating immune responses to vaccines as well as other immunotherapeutic strategies...
  65. ncbi Rapid CD4+ T-lymphocyte depletion in rhesus monkeys infected with a simian-human immunodeficiency virus expressing the envelope glycoproteins of a primary dual-tropic Ethiopian Clade C HIV type 1 isolate
    Mark Cayabyab
    Department of Cancer Immunology/AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA
    AIDS Res Hum Retroviruses 20:27-40. 2004
    ..The ability to cause rapid and profound loss of CD4(+) T lymphocytes in vivo is a property shared by passaged, CXCR4-using SHIVs, irrespective of the clade of origin of the HIV-1 envelope glycoproteins...
  66. ncbi Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with Gag epitope cytotoxic T-lymphocyte escape mutations
    Wendy W Yeh
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Ave, Boston, MA 02215, USA
    J Virol 80:8168-77. 2006
    ....
  67. ncbi Gender differences in human immunodeficiency virus type 1-specific CD8 responses in the reproductive tract and colon following nasal peptide priming and modified vaccinia virus Ankara boosting
    James W Peacock
    Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
    J Virol 78:13163-72. 2004
    ..Understanding the cellular and molecular basis of gender-determined immune responses will be important for optimizing induction of anti-HIV-1 mucosal immune responses in both males and females...
  68. ncbi A human T-cell leukemia virus type 1 regulatory element enhances the immunogenicity of human immunodeficiency virus type 1 DNA vaccines in mice and nonhuman primates
    Dan H Barouch
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 79:8828-34. 2005
    ..This strategy could therefore be explored as a potential method to enhance DNA vaccine immunogenicity in humans...
  69. ncbi Fitness costs limit viral escape from cytotoxic T lymphocytes at a structurally constrained epitope
    Fred W Peyerl
    Harvard Medical School, Beth Israel Deaconess Medical Center, Division of Viral Pathogenesis, Research East Room 113, 330 Brookline Ave, Boston, MA 02215, USA
    J Virol 78:13901-10. 2004
    ....
  70. ncbi A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys
    Sampa Santra
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:10489-94. 2008
    ..These findings suggest that immunization with centralized genes is a promising vaccine strategy for developing a global vaccine for HIV-1 as well as vaccines for other genetically diverse viruses...
  71. ncbi Neutralizing antibodies and CD8+ T lymphocytes both contribute to immunity to adenovirus serotype 5 vaccine vectors
    Shawn M Sumida
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 78:2666-73. 2004
    ..Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both humoral and cellular Ad5-specific immune responses...
  72. ncbi Identification of T lymphocytes in simian immunodeficiency virus encephalitis: distribution of CD8+ T cells in association with central nervous system vessels and virus
    Woong-Ki Kim
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurovirol 10:315-25. 2004
    ..These data suggest that in brains of SIV-infected monkeys and HIV-infected humans, CD8+ T lymphocytes traffic to and are retained in the CNS in an angiocentric and possibly antigen-specific manner...
  73. ncbi Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques
    Jörn E Schmitz
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, RE 113, 330 Brookline Ave, Boston, Massacusetts 02215, USA
    J Virol 79:8131-41. 2005
    ....
  74. ncbi Adaptive immune response of Vgamma2Vdelta2 T cells: a new paradigm
    Zheng W Chen
    Tuberculosis Research Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RE113 RE216, Boston, MA 02115, USA
    Trends Immunol 24:213-9. 2003
    ....
  75. ncbi Vgamma2Vdelta2+ T cells and anti-microbial immune responses
    Zheng W Chen
    Tuberculosis Research Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, RE 113 213C, Boston MA 02115, USA
    Microbes Infect 5:491-8. 2003
    ..Recent studies have demonstrated that this unique gammadelta T cell subpopulation can be a component of adaptive immune responses and contribute to anti-microbial immunity to infections...
  76. ncbi Viral escape from dominant simian immunodeficiency virus epitope-specific cytotoxic T lymphocytes in DNA-vaccinated rhesus monkeys
    Dan H Barouch
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 77:7367-75. 2003
    ..These data suggest that CTL exert selective pressure on viral replication and that viral escape from CTL may be a limitation of CTL-based AIDS vaccine strategies...
  77. ncbi Non-classical natural killer T cells modulate plasmid DNA vaccine antigen expression and vaccine-elicited immune responses by MCP-1 secretion after interaction with a beta2-microglobulin-independent CD1d
    Ralf Geiben-Lynn
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 284:33800-6. 2009
    ..Manipulation of NKT cell function or co-administration of MCP-1 may represent novel methods for enhancing immune responses to plasmid DNA vaccines...
  78. ncbi Limited contribution of mucosal IgA to Simian immunodeficiency virus (SIV)-specific neutralizing antibody response and virus envelope evolution in breast milk of SIV-infected, lactating rhesus monkeys
    Sallie R Permar
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Virol 84:8209-18. 2010
    ....
  79. ncbi Preservation of memory CD4(+) T lymphocytes in breast milk of lactating rhesus monkeys during acute simian immunodeficiency virus infection
    Sallie R Permar
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    J Infect Dis 201:302-10. 2010
    ..Interestingly, the number and proportion of effector CD8(+) T lymphocytes in milk were increased during acute SIV infection, suggesting effective control of virus-mediated CD4(+) T lymphocyte destruction in the breast milk compartment...
  80. ncbi Strategies for an HIV vaccine
    Norman L Letvin
    Harvard Medical School, Beth Israel Deaconess Medical Center, 41 Avenue Louis Pasteur, RE-113, Boston, MA 02215, USA
    J Clin Invest 110:15-20. 2002
  81. ncbi High frequency of virus-specific B lymphocytes in germinal centers of simian-human immunodeficiency virus-infected rhesus monkeys
    David H Margolin
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 76:3965-73. 2002
    ..This extraordinarily high frequency of Env-specific B lymphocytes suggests that the expansion of virus-specific B cells may largely account for the follicular hyperplasia in AIDS virus-infected individuals...
  82. ncbi Prospects for vaccine protection against HIV-1 infection and AIDS
    Norman L Letvin
    Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Annu Rev Immunol 20:73-99. 2002
    ..We then describe vaccine strategies that have been explored and discuss the evidence suggesting that cellular immune responses elicited by novel vaccine modalities may attenuate clinical disease caused by HIV-1...
  83. ncbi Association of prolonged survival in HLA-A2+ progressive multifocal leukoencephalopathy patients with a CTL response specific for a commonly recognized JC virus epitope
    Igor J Koralnik
    Neurology Department, Beth Israel Deaconess Medical Center, RE 213B, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215
    J Immunol 168:499-504. 2002
    ..These data suggest that the JCV-specific cellular immune response may be important in the containment of PML, and the tetramer-staining assay may provide a useful prognostic tool in the clinical management of these patients...
  84. ncbi Plasmid chemokines and colony-stimulating factors enhance the immunogenicity of DNA priming-viral vector boosting human immunodeficiency virus type 1 vaccines
    Dan H Barouch
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Virol 77:8729-35. 2003
    ..These data demonstrate that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity...
  85. ncbi Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses
    Keith A Reimann
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    J Virol 79:8878-85. 2005
    ....
  86. ncbi Expression kinetics of the interleukin-2/immunoglobulin (IL-2/Ig) plasmid cytokine adjuvant
    Dan H Barouch
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    Vaccine 22:3092-7. 2004
    ....
  87. ncbi Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants
    Dan H Barouch
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nat Immunol 6:247-52. 2005
    ....
  88. ncbi HIV escape from cytotoxic T lymphocytes: a potential hurdle for vaccines?
    Dan H Barouch
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Lancet 364:10-1. 2004
  89. ncbi Standardized assessment of NAb responses elicited in rhesus monkeys immunized with single- or multi-clade HIV-1 envelope immunogens
    Michael S Seaman
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Ave RE 204, Boston, MA 02215, USA
    Virology 367:175-86. 2007
    ....
  90. ncbi Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity
    Dan H Barouch
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Immunol 172:6290-7. 2004
    ..Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity...
  91. ncbi Use of an anti-CD16 antibody for in vivo depletion of natural killer cells in rhesus macaques
    Elisa I Choi
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Immunology 124:215-22. 2008
    ..These studies describe a non-human primate model for in vivo NK-cell depletion and suggest a limited role for cytotoxic CD16(+) NK cells in controlling AIDS virus replication during chronic infection...
  92. ncbi Kinetics of recombinant adenovirus type 5, vaccinia virus, modified vaccinia ankara virus, and DNA antigen expression in vivo and the induction of memory T-lymphocyte responses
    Ralf Geiben-Lynn
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Clin Vaccine Immunol 15:691-6. 2008
    ....
  93. ncbi CD4+ T lymphocytes mediate in vivo clearance of plasmid DNA vaccine antigen expression and potentiate CD8+ T-cell immune responses
    Ralf Geiben-Lynn
    Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    Blood 112:4585-90. 2008
    ..These data demonstrate a dominant role of CD4(+) T cell-mediated cytotoxicity in plasmid DNA vaccine antigen clearance...
  94. ncbi Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice
    Feng Gao
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    AIDS Res Hum Retroviruses 19:817-23. 2003
    ....
  95. ncbi Anti-gamma interferon antibodies enhance the immunogenicity of recombinant adenovirus vectors
    Shawn S Jackson
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Clin Vaccine Immunol 18:1969-78. 2011
    ..These observations illustrate the utility of an anti-IFN-? Ab for potentiating rAd immunizations to effect quantitative and qualitative changes in the effector and memory CTL populations...
  96. ncbi The TRIM5 gene modulates penile mucosal acquisition of simian immunodeficiency virus in rhesus monkeys
    Wendy W Yeh
    Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    J Virol 85:10389-98. 2011
    ..In addition, we used our understanding of TRIM5 to establish a novel nonhuman primate penile transmission model for AIDS mucosal pathogenesis and vaccine research...
  97. ncbi Antibody-dependent cell-mediated cytotoxicity in simian immunodeficiency virus-infected rhesus monkeys
    Yue Sun
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Science, 330 Brookline Avenue, Boston, MA 02115, USA
    J Virol 85:6906-12. 2011
    ..This final observation raises the possibility that the antibodies that mediate ADCC are a subset of the antibodies detected in a binding assay and arise within weeks of infection...
  98. ncbi Epitope-specific CD8+ T lymphocytes cross-recognize mutant simian immunodeficiency virus (SIV) sequences but fail to contain very early evolution and eventual fixation of epitope escape mutations during SIV infection
    Evan M Cale
    Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E CLS 1043, Boston, MA 02215, USA
    J Virol 85:3746-57. 2011
    ....
  99. ncbi Envelope vaccination shapes viral envelope evolution following simian immunodeficiency virus infection in rhesus monkeys
    Aravind Basavapathruni
    Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
    J Virol 84:953-63. 2010
    ..These data show that env vaccination altered the focus of the antibody-mediated selection pressure on the evolution of envelope following SIV challenge...
  100. ncbi Novel adeno-associated virus vector vaccine restricts replication of simian immunodeficiency virus in macaques
    Philip R Johnson
    Columbus Children s Hospital, Room WA3011, 700 Children s Dr, Columbus, OH 43205, USA
    J Virol 79:955-65. 2005
    ..These data suggest that rAAV vaccine vectors induced biologically relevant immune responses, and thus, warrant continued development as a viable HIV-1 vaccine candidate...

Research Grants16

  1. IMMUNOREGULATION IN AIDS
    Norman Letvin; Fiscal Year: 2007
    ..C. Fitness relative to wild type viruses. 3. Nondominant SHIV epitope-specific CTL populations. A. Breadth and magnitude. B. Functional repertoire. C. TCR repertoire. 4. Nondominant epitope-specific CTL and control of SIV replication. ..
  2. Conference HIV Vaccine Development Progress & Prospects
    Norman Letvin; Fiscal Year: 2004
    ..abstract_text> ..
  3. DNA VACCINE IMMUNITY TO HIV1 AND SIV
    Norman Letvin; Fiscal Year: 2002
    ..This aim therefore studies cross reactivity to a single epitope not multi epitopes. ..