David Watkins

Summary

Affiliation: University of Wisconsin
Country: USA

Publications

  1. pmc Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with dna and recombinant adenoviral vaccine vectors expressing Gag
    Danilo R Casimiro
    Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck and Co, West Point, Pennsylvania 19486, USA
    J Virol 79:15547-55. 2005
  2. pmc AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape
    Nicholas J Maness
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Exp Med 204:2505-12. 2007
  3. pmc GagCM9-specific CD8+ T cells expressing limited public TCR clonotypes do not suppress SIV replication in vivo
    Lara Vojnov
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, Wisconsin, United States of America
    PLoS ONE 6:e23515. 2011
  4. pmc Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans
    David I Watkins
    Wisconsin National Primate Research Center, University of Wisconsin Madison, 1220 Capitol Court, Madison, Wisconsin 53715, USA
    Nat Med 14:617-21. 2008
  5. pmc The hope for an HIV vaccine based on induction of CD8+ T lymphocytes--a review
    David I Watkins
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI, USA
    Mem Inst Oswaldo Cruz 103:119-29. 2008
  6. pmc CD8+ T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in vivo, and many revert after transmission
    Philip A Mudd
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 85:12804-10. 2011
  7. pmc Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression follow
    Helen Horton
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 76:7187-202. 2002
  8. pmc The antiviral efficacy of simian immunodeficiency virus-specific CD8+ T cells is unrelated to epitope specificity and is abrogated by viral escape
    John T Loffredo
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 81:2624-34. 2007
  9. ncbi request reprint Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression
    Jonah B Sacha
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Immunol 178:2746-54. 2007
  10. pmc Simian immunodeficiency virus-specific CD4+ T cells from successful vaccinees target the SIV Gag capsid
    Juan P Giraldo-Vela
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53711, USA
    Immunogenetics 62:701-7. 2010

Research Grants

  1. The Functional Significance of Cytotoxic T Lymphocyte Escape
    David Watkins; Fiscal Year: 2007
  2. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David I Watkins; Fiscal Year: 2010
  3. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2007
  4. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2007
  5. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2007
  6. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2006
  7. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2006
  8. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2006
  9. The Functional Significance of CTL Escape
    David Watkins; Fiscal Year: 2006
  10. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2005

Detail Information

Publications89

  1. pmc Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with dna and recombinant adenoviral vaccine vectors expressing Gag
    Danilo R Casimiro
    Department of Vaccines and Biologics Research, Merck Research Laboratories, Merck and Co, West Point, Pennsylvania 19486, USA
    J Virol 79:15547-55. 2005
    ..However, virus control was short-lived, and indications of viral escape were evident as early as 6 months postinfection. The implications of these results in vaccine design and clinical testing are discussed...
  2. pmc AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape
    Nicholas J Maness
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Exp Med 204:2505-12. 2007
    ..The discovery of an immunodominant CD8-TL response in elite controller macaques against a cryptic epitope suggests that the AIDS virus-specific cellular immune response is likely far more complex than is generally assumed...
  3. pmc GagCM9-specific CD8+ T cells expressing limited public TCR clonotypes do not suppress SIV replication in vivo
    Lara Vojnov
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, Wisconsin, United States of America
    PLoS ONE 6:e23515. 2011
    ..It is possible that these seven animals failed to control viral replication because of the narrow TCR repertoire expressed by the GagCM9-specific CD8(+) T cell population elicited by vaccination and infection...
  4. pmc Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans
    David I Watkins
    Wisconsin National Primate Research Center, University of Wisconsin Madison, 1220 Capitol Court, Madison, Wisconsin 53715, USA
    Nat Med 14:617-21. 2008
    ..Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge...
  5. pmc The hope for an HIV vaccine based on induction of CD8+ T lymphocytes--a review
    David I Watkins
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI, USA
    Mem Inst Oswaldo Cruz 103:119-29. 2008
    ..This would be somewhat analogous to control of virus replication by triple drug therapy or neutralizing antibodies...
  6. pmc CD8+ T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in vivo, and many revert after transmission
    Philip A Mudd
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 85:12804-10. 2011
    ..Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine...
  7. pmc Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell responses and reduces initial viral replication but does not prevent disease progression follow
    Helen Horton
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 76:7187-202. 2002
    ..01). However, despite the induction of virus-specific cellular immune responses and reduced peak viral loads, most animals still suffered from gradual CD4 depletion and progressed to disease...
  8. pmc The antiviral efficacy of simian immunodeficiency virus-specific CD8+ T cells is unrelated to epitope specificity and is abrogated by viral escape
    John T Loffredo
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 81:2624-34. 2007
    ..Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for an HIV vaccine...
  9. ncbi request reprint Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression
    Jonah B Sacha
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Immunol 178:2746-54. 2007
    ..0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag...
  10. pmc Simian immunodeficiency virus-specific CD4+ T cells from successful vaccinees target the SIV Gag capsid
    Juan P Giraldo-Vela
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53711, USA
    Immunogenetics 62:701-7. 2010
    ..Analysis of SIV-specific CD4+ T-cell responses elicited by a successful vaccine may have important implications in the understanding of vaccine design...
  11. pmc Tat-vaccinated macaques do not control simian immunodeficiency virus SIVmac239 replication
    Todd M Allen
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 76:4108-12. 2002
    ..Despite the induction of Tat-specific CTL, there was no significant reduction in either peak or viral set point compared to that of controls...
  12. pmc Relevance of studying T cell responses in SIV-infected rhesus macaques
    Laura E Valentine
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI, 53711 USA
    Trends Microbiol 16:605-11. 2008
    ..The best animal model available to explore such issues is simian immunodeficiency virus infection of rhesus macaques, which serves as the primary proving ground for AIDS vaccines...
  13. ncbi request reprint Analysis of the immune response and viral evolution during the acute phase of SIV infection
    Helen Horton
    Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol City, Madison, WI 53715 1299, USA
    Vaccine 20:1927-32. 2002
    ....
  14. pmc Infection with "escaped" virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques
    Laura E Valentine
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, Wisconsin 53706, USA
    J Virol 83:11514-27. 2009
    ..04). Our results suggest that these epitope-specific CD8+ T-cell responses may play a role in establishing the control of viral replication in Mamu-B*08+ macaques...
  15. ncbi request reprint Initiation of antiretroviral therapy during chronic SIV infection leads to rapid reduction in viral loads and the level of T-cell immune response
    Jean D Boyer
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    J Med Primatol 35:202-9. 2006
    ..The results are important for understanding SIV disease progression in different MHC Mamu alleles and also for improving the interpretation and quality of pre-clinical studies in rhesus monkeys...
  16. pmc Synchronous infection of SIV and HIV in vitro for virology, immunology and vaccine-related studies
    Jonah B Sacha
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, Wisconsin, USA
    Nat Protoc 5:239-46. 2010
    ..Once a virus stock is generated, magnetofection of target cells is rapid, requiring only 1-2 h. Here we present a detailed protocol for this assay and review its applications for studying the immune response to HIV...
  17. ncbi request reprint Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection
    DAVID H O'CONNOR
    Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA
    Nat Med 8:493-9. 2002
    ..Our results suggest that acute viral escape from CTLs is a hallmark of SIV infection and that CTLs with high functional avidity can rapidly select for escape variants...
  18. pmc Effective simian immunodeficiency virus-specific CD8+ T cells lack an easily detectable, shared characteristic
    Lara Vojnov
    Department of Pathology, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 84:753-64. 2010
    ..Our results suggest that a single definitive correlate of immune control may not exist; rather, a successful CD8(+) T-cell response may be comprised of several factors...
  19. pmc Repeated low-dose mucosal simian immunodeficiency virus SIVmac239 challenge results in the same viral and immunological kinetics as high-dose challenge: a model for the evaluation of vaccine efficacy in nonhuman primates
    Adrian B McDermott
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, Wisconsin, USA
    J Virol 78:3140-4. 2004
    ..This low-dose repeated challenge may be a valuable tool in the evaluation of potential vaccine regimes and offers a more physiologically relevant regimen for pathogenic SIVmac239 challenge experiments...
  20. ncbi request reprint Differences between T cell epitopes recognized after immunization and after infection
    Thorsten U Vogel
    Wisconsin National Primate Research Center, University of Wisconsin, 1220 Capital Court, Madison, WI 53715, USA
    J Immunol 169:4511-21. 2002
    ..The repertoire of the immune response detected in the peripheral blood after immunization substantially differed from the immune response detected in the peripheral blood after infection...
  21. ncbi request reprint Reversion of CTL escape-variant immunodeficiency viruses in vivo
    Thomas C Friedrich
    Wisconsin National Primate Research Center, Madison, Wisconsin 53715, USA
    Nat Med 10:275-81. 2004
    ..In the absence of selective pressure upon transmission to new hosts, these original escape mutations can be lost. This suggests that some HIV CTL epitopes will be maintained in human populations...
  22. pmc Tat(28-35)SL8-specific CD8+ T lymphocytes are more effective than Gag(181-189)CM9-specific CD8+ T lymphocytes at suppressing simian immunodeficiency virus replication in a functional in vitro assay
    John T Loffredo
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53715, USA
    J Virol 79:14986-91. 2005
    ..Such differences in antigen-specific CD8+-T-lymphocyte efficacy may be important for selecting CD8+ T lymphocyte epitopes for inclusion in future HIV vaccines...
  23. pmc Pol-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells prior to Nef-mediated major histocompatibility complex class I downregulation
    Jonah B Sacha
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 81:11703-12. 2007
    ..Finally, Pol-specific CD8+ T cells eliminated infected cells as early as 6 h postinfection, well before MHC-I downregulation, suggesting a previously underappreciated antiviral role for Pol-specific CD8+ T cells...
  24. ncbi request reprint Immunogenicity of hybrid DNA vaccines expressing hepatitis B core particles carrying human and simian immunodeficiency virus epitopes in mice and rhesus macaques
    Deborah Heydenburg Fuller
    PowderJect Vaccines Inc, Madison, WI 53562, USA
    Virology 364:245-55. 2007
    ..These data demonstrate that immunization with hybrid HBcAg-epitope DNA vaccines is an effective strategy to increase the magnitude and breadth of HIV-specific CTL responses...
  25. pmc Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection
    Bianca R Mothe
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 76:875-84. 2002
    ..In most of the Mamu-A*01-positive macaques tested, CTL responses against epitopes bound by Mamu-A*01 dominated the CD8(+) cellular immune response...
  26. pmc Expression of the major histocompatibility complex class I molecule Mamu-A*01 is associated with control of simian immunodeficiency virus SIVmac239 replication
    Bianca R Mothe
    Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, WI 53715 1299, USA
    J Virol 77:2736-40. 2003
    ..Of the common MHC class I alleles, animals that expressed Mamu-A*01 exhibited the best control of viral replication...
  27. pmc Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239
    Thorsten U Vogel
    Wisconsin Primate Research Center Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 77:13348-60. 2003
    ....
  28. pmc Escape in one of two cytotoxic T-lymphocyte epitopes bound by a high-frequency major histocompatibility complex class I molecule, Mamu-A*02: a paradigm for virus evolution and persistence?
    Thorsten U Vogel
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715, USA
    J Virol 76:11623-36. 2002
    ..Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection...
  29. pmc Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques
    Myrna C Bonaldo
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 84:3699-706. 2010
    ..These recombinant YF17D-induced SIV-specific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells...
  30. pmc Not all cytokine-producing CD8+ T cells suppress simian immunodeficiency virus replication
    Chungwon Chung
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, Wisconsin 53715 1299, USA
    J Virol 81:1517-23. 2007
    ..Interestingly, in vitro suppression efficacy was not always associated with the ability to produce gamma interferon, tumor necrosis factor alpha, or interleukin-2...
  31. pmc Comprehensive immunological evaluation reveals surprisingly few differences between elite controller and progressor Mamu-B*17-positive simian immunodeficiency virus-infected rhesus macaques
    Nicholas J Maness
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, Wisconsin 53711, USA
    J Virol 82:5245-54. 2008
    ..Most importantly, our data indicate that the important differences between Mamu-B*17-positive ECs and progressors are not readily discernible using standard assays to measure immune responses...
  32. pmc Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection
    Todd M Allen
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715, USA
    J Virol 76:10507-11. 2002
    ..By themselves, these strong CTL responses failed to control SIVmac239 replication...
  33. pmc Patterns of CD8+ immunodominance may influence the ability of Mamu-B*08-positive macaques to naturally control simian immunodeficiency virus SIVmac239 replication
    John T Loffredo
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 82:1723-38. 2008
    ..Natural containment of AIDS virus replication in Mamu-B*08-positive macaques may, therefore, be related to a combination of immunodominance and viral escape from CD8(+) T-cell responses...
  34. pmc T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge
    Mauricio A Martins
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 84:4352-65. 2010
    ..Furthermore, the present study demonstrates that certain viral proteins may be more effective than others as vaccine immunogens...
  35. pmc Robust, vaccine-induced CD8(+) T lymphocyte response against an out-of-frame epitope
    Nicholas J Maness
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53706, USA
    J Immunol 184:67-72. 2010
    ..Our data demonstrate both that the pathway from vaccination to immune response is not well understood and that products of alternate reading frames may be rich and untapped sources of T cell epitopes...
  36. pmc Consequences of cytotoxic T-lymphocyte escape: common escape mutations in simian immunodeficiency virus are poorly recognized in naive hosts
    Thomas C Friedrich
    Wisconsin National Primate Research Center, 1220 Capitol Court, Madison, WI 53715, USA
    J Virol 78:10064-73. 2004
    ..Moreover, since the mutant epitope sequences did not revert to wild type during the study period, it is possible that low-frequency CTL exerted enough selective pressure to preserve epitope mutations in viruses replicating in vivo...
  37. pmc Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses
    DAVID H O'CONNOR
    Wisconsin Regional Primate Research Center and Department of Pathology and Laboratory Medicine, Madison, Wisconsin, USA
    J Virol 77:9029-40. 2003
    ....
  38. pmc Simian immunodeficiency virus-specific CD8+ T cells recognize Vpr- and Rev-derived epitopes early after infection
    Jonah B Sacha
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 84:10907-12. 2010
    ..These studies show for the first time that Vpr- and Rev-specific CD8(+) T cells recognize and kill simian immunodeficiency virus (SIV)-infected CD4(+) T cells early after SIV infection...
  39. pmc CD8+ T cell recognition of cryptic epitopes is a ubiquitous feature of AIDS virus infection
    Nicholas J Maness
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, WI 53711, USA
    J Virol 84:11569-74. 2010
    ..The epitopes were targeted by high-frequency responses as early as 2 weeks postinfection and in the chronic phase. Hence, previously overlooked ARF-encoded epitopes could be important components of AIDS vaccines...
  40. ncbi request reprint Molecular typing of major histocompatibility complex class I alleles in the Indian rhesus macaque which restrict SIV CD8+ T cell epitopes
    Masahiko Kaizu
    Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA
    Immunogenetics 59:693-703. 2007
    ..Furthermore, application of this technically simple and accurate typing method should facilitate selection, utilization, and breeding of rhesus macaques for AIDS virus pathogenesis and vaccine studies...
  41. pmc Mamu-B*08-positive macaques control simian immunodeficiency virus replication
    John T Loffredo
    Wisconsin National Primate Research Center, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 81:8827-32. 2007
    ..002). Mamu-B*08-positive macaques may, therefore, provide a good model to understand the correlates of MHC class I allele-associated immune protection and viral containment in human elite controllers...
  42. pmc The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers
    Juan P Giraldo-Vela
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 82:859-70. 2008
    ..0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design...
  43. pmc CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation
    John T Loffredo
    Wisconsin National Primate Research Center WNPRC, University of Wisconsin Madison, Madison, Wisconsin, United States of America
    PLoS ONE 2:e1152. 2007
    ..SIV replication was rapidly controlled with the reappearance of CD8+ cells, implicating that these cells actively suppress viral replication in ECs...
  44. ncbi request reprint Cytotoxic T-lymphocyte escape monitoring in simian immunodeficiency virus vaccine challenge studies
    DAVID H O'CONNOR
    University of Wisconsin at Madison, Department of Pathology, Madison, Wisconsin 53709, USA
    DNA Cell Biol 21:659-64. 2002
    ..To illustrate the importance of escape analysis, we show that rapid emergence of escape variants postchallenge contributed to the failure of a DNA prime/MVA boost vaccine regimen encoding SIV Tat...
  45. pmc Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge
    Matthew R Reynolds
    AIDS Vaccine Research Laboratory, 555 Science Dr, Madison, WI 53711, USA
    J Virol 84:9190-9. 2010
    ..Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication...
  46. ncbi request reprint HIV vaccine development
    David I Watkins
    Department of Pathology, University of Wisconsin Madison, Madison, WI, USA
    Top HIV Med 18:35-6. 2010
    ..All of these promising results should serve to energize the HIV vaccine field...
  47. pmc Vaccine-induced cellular responses control simian immunodeficiency virus replication after heterologous challenge
    Nancy A Wilson
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Madison, Wisconsin 53711, USA
    J Virol 83:6508-21. 2009
    ....
  48. pmc Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection
    Jonah B Sacha
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715, USA
    Proc Natl Acad Sci U S A 106:9791-6. 2009
    ..These results suggest that retrovirus-specific CD4(+) T cells may contribute directly to elite control by inhibiting viral replication in macrophages...
  49. pmc Novel translation products from simian immunodeficiency virus SIVmac239 Env-encoding mRNA contain both Rev and cryptic T-cell epitopes
    Nicholas J Maness
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Drive, Madison, WI 53711, USA
    J Virol 83:10280-5. 2009
    ..Our data suggest that the translation of viral alternate reading frames may be an important source of T-cell epitopes, including epitopes normally derived from functional proteins...
  50. pmc Is an HIV vaccine possible?
    Nancy A Wilson
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, Wisconsin 53711, USA
    Braz J Infect Dis 13:304-10. 2009
    ..This review will focus on recent developments in HIV vaccine development. We will deal largely with attempts to develop a T cell-based vaccine using the non-human primate SIV challenge model...
  51. pmc Macaques vaccinated with live-attenuated SIV control replication of heterologous virus
    Matthew R Reynolds
    AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53715, USA
    J Exp Med 205:2537-50. 2008
    ....
  52. ncbi request reprint Characterization of the peptide-binding specificity of Mamu-B*17 and identification of Mamu-B*17-restricted epitopes derived from simian immunodeficiency virus proteins
    Bianca R Mothe
    Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715, USA
    J Immunol 169:210-9. 2002
    ..Furthermore, it is an important step toward the design of a multiepitope vaccine for SIV and HIV...
  53. pmc The high-frequency major histocompatibility complex class I allele Mamu-B*17 is associated with control of simian immunodeficiency virus SIVmac239 replication
    Levi J Yant
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Virol 80:5074-7. 2006
    ..001). Mamu-B(*)17-positive macaques could, therefore, facilitate our understanding of the correlates of viral control...
  54. pmc Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239
    Nancy A Wilson
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53711, USA
    J Virol 80:5875-85. 2006
    ....
  55. ncbi request reprint Polymorphisms in eight host genes associated with control of HIV replication do not mediate elite control of viral replication in SIV-infected Indian rhesus macaques
    Andrea Weiler
    Wisconsin National Primate Research Center, University of Wisconsin Madison, Madison, WI 53715, USA
    Immunogenetics 58:1003-9. 2006
    ..We did not detect any correlations between plasma viral concentration and polymorphisms in host genes examined in this study. In addition, we did not find the polymorphisms present in humans in any of our macaques...
  56. ncbi request reprint The high frequency Indian rhesus macaque MHC class I molecule, Mamu-B*01, does not appear to be involved in CD8+ T lymphocyte responses to SIVmac239
    John T Loffredo
    Wisconsin National Primate Research Center WNPRC, University of Wisconsin, Madison, WI 53715, USA
    J Immunol 175:5986-97. 2005
    ..Our results suggest that the high frequency MHC class I molecule, Mamu-B*01, is not involved in SIV-specific CD8+ T lymphocyte responses...
  57. pmc Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication
    Thomas C Friedrich
    Wisconsin National Primate Research Center, 1220 Capitol Court, Madison, WI 53715 1299, USA
    J Virol 81:3465-76. 2007
    ..It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control...
  58. pmc A dominant role for CD8+-T-lymphocyte selection in simian immunodeficiency virus sequence variation
    DAVID H O'CONNOR
    Wisconsin Primate Research Center, Department of Pathology, Laboratoty of Medicine, University of Wisconsin, 1300 University Ave, Madison, WI 53706, USA
    J Virol 78:14012-22. 2004
    ..We also found that >60% of viral variation outside of the viral envelope occurs within recognized CD8-TL epitopes. Therefore, we conclude that CD8-TL selection is the dominant cause of SIV diversification outside of the envelope...
  59. pmc The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques--implications for recombinant vaccine design
    Philip A Mudd
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    Immunogenetics 62:593-600. 2010
    ..The data also suggest potential immunogenic regions of YF17D that could serve as the focus of recombinant T cell vaccine development...
  60. pmc Two MHC class I molecules associated with elite control of immunodeficiency virus replication, Mamu-B*08 and HLA-B*2705, bind peptides with sequence similarity
    John T Loffredo
    Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706, USA
    J Immunol 182:7763-75. 2009
    ....
  61. pmc Extraepitopic compensatory substitutions partially restore fitness to simian immunodeficiency virus variants that escape from an immunodominant cytotoxic-T-lymphocyte response
    Thomas C Friedrich
    Wisconsin National Primate Research Center, Madison, Wisconsin 53715, USA
    J Virol 78:2581-5. 2004
    ..The extraepitopic mutations partially restore in vitro replicative fitness of viruses bearing the escape mutations. Constraints on epitope sequences may therefore play a role in determining the rate of escape from CTL responses in vivo...
  62. pmc Recognition of escape variants in ELISPOT does not always predict CD8+ T-cell recognition of simian immunodeficiency virus-infected cells expressing the same variant sequences
    Laura E Valentine
    Wisconsin National Primate Research Center, Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA
    J Virol 82:575-81. 2008
    ..Our results indicate that "cross-reactive" CD8(+) T-cell responses identified in ELISPOT and ICS assays using a single high concentration of variant peptide often fail to predict the recognition of cells infected with variant viruses...
  63. pmc Differential antigen presentation kinetics of CD8+ T-cell epitopes derived from the same viral protein
    Jonah B Sacha
    Wisconsin National Primate Research Center WNPRC, Madison, WI 53711, USA
    J Virol 82:9293-8. 2008
    ..These results illustrate that significant differences in presentation kinetics can exist among CD8+ T-cell epitopes derived from the same viral protein...
  64. ncbi request reprint Highlights of the 15th Conference on Retroviruses and Opportunistic Infections. Basic HIV vaccine development
    David I Watkins
    Department of Pathology, AIDS Vaccine Research Laboratory, University of Wisconsin Madison, Madison, WI, USA
    Top HIV Med 16:7-8. 2008
    ..This will likely herald a new era in HIV vaccine research, resulting in a redoubling of effort to uncover innovative new ways of making an HIV vaccine...
  65. pmc Reduction of CD4+ T cells in vivo does not affect virus load in macaque elite controllers
    Philip A Mudd
    Department of Pathology and Laboratory Medicine, University of Wisconsin Madison, 555 Science Dr, Madison, WI 53711, USA
    J Virol 85:7454-9. 2011
    ..Viral loads remained stable throughout the experiment, suggesting that SIV-specific CD4(+) T cell responses may not play a direct role in controlling chronic viral replication in these elite controllers...
  66. ncbi request reprint HIV Vaccine Development
    David I Watkins
    Department of Pathology, University of Wisconsin Madison, Madison, WI, USA
    Top HIV Med 17:35-6. 2009
    ..Finally, adeno-associated-virus-derived neutralizing antibodies completely protected macaques from infection, suggesting novel mechanisms of viral control...
  67. ncbi request reprint Identification of seventeen new simian immunodeficiency virus-derived CD8+ T cell epitopes restricted by the high frequency molecule, Mamu-A*02, and potential escape from CTL recognition
    John T Loffredo
    National Primate Research Center, University of Wisconsin WPRC, Madison 53715, USA
    J Immunol 173:5064-76. 2004
    ..This work enhances the use of the SIV-infected macaque model for HIV and increases our understanding of the breadth of CD8+ T cell responses in SIV infection...
  68. ncbi request reprint HIV and SIV CTL escape: implications for vaccine design
    Philip J R Goulder
    Department of Paediatrics, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, UK
    Nat Rev Immunol 4:630-40. 2004
  69. pmc Long-term control of simian immunodeficiency virus replication with central memory CD4+ T-cell preservation after nonsterile protection by a cytotoxic T-lymphocyte-based vaccine
    Miki Kawada
    International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Virol 81:5202-11. 2007
    ..Our results suggest that prophylactic CTL vaccine-based nonsterile protection can result in long-term viral containment by adapted CTL responses for AIDS prevention...
  70. pmc Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial
    Tetsuro Matano
    Department of Microbiology, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Exp Med 199:1709-18. 2004
    ..Our results indicate that vaccine induction of highly effective CTLs can result in the containment of replication of a highly pathogenic immunodeficiency virus...
  71. ncbi request reprint Public health. A sound rationale needed for phase III HIV-1 vaccine trials
    Dennis R Burton
    Scripps Research Institute, La Jolla, California, USA
    Science 303:316. 2004
  72. ncbi request reprint Emergence of cytotoxic T lymphocyte escape mutants following antiretroviral treatment suspension in rhesus macaques infected with SIVmac251
    Janos Nacsa
    National Cancer Institute, Basic Research Laboratory, 41 D804, Bethesda, Maryland 20892, USA
    Virology 305:210-8. 2003
    ..In addition, these data also suggest that interruption of therapy may be less effective in chronic infection because of preexisting immune escape and that immune escape is a risk of interruption of therapy...
  73. pmc Prevention of disease induced by a partially heterologous AIDS virus in rhesus monkeys by using an adjuvanted multicomponent protein vaccine
    Gerald Voss
    GlaxoSmithKline Biologicals, Rixensart, Belgium
    J Virol 77:1049-58. 2003
    ..Furthermore, vaccination prevented the development of AIDS for more than 2.5 years. The combination of the regulatory proteins Nef and Tat together with the structural protein gp120 was required for vaccine efficacy...
  74. ncbi request reprint Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric Env protein boost in the SHIV rhesus macaque model
    Patricia L Earl
    Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA
    Virology 294:270-81. 2002
    ..Thus, immunization with MVA/SHIV89.6 alone or with a protein boost stimulated both arms of the immune system and resulted in significant control of viremia and delayed progression to disease after challenge with SHIV-89.6P...
  75. pmc Analysis of pigtail macaque major histocompatibility complex class I molecules presenting immunodominant simian immunodeficiency virus epitopes
    Miranda Z Smith
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia
    J Virol 79:684-95. 2005
    ..nemestrina MHC class I allele restricting a functionally important immunodominant SIV Gag epitope establishes a basis for studying CD8+ T-cell responses against AIDS in an important, widely available nonhuman primate species...
  76. ncbi request reprint MHC polymorphism: AIDS susceptibility in non-human primates
    Ronald E Bontrop
    Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, P O Box 3306, 2280 GH Rijswijk, The Netherlands
    Trends Immunol 26:227-33. 2005
    ....
  77. ncbi request reprint HIV pathogenesis: the first cut is the deepest
    Louis J Picker
    Nat Immunol 6:430-2. 2005
  78. ncbi request reprint Identification and characterization of previously described epitopes in HIV-1 subtypes B, C, F and BF in Brazil
    Artur Trancoso Lopo de Queiroz
    Advanced Public Health Laboratory, Gonçalo Moniz Research Center, Oswaldo Cruz Foundation, Salvador, BA, Brazil
    Braz J Infect Dis 11:27-30. 2007
    ..Interestingly, ds/dn analyses showed evidence of purifying selective pressure. These types of analyses could be useful for the assessment of possible vaccine efficiency in populations...
  79. ncbi request reprint Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection
    Jacob D Estes
    Department of Microbiology, Medical School, University of Minnesota, Minneapolis 55455, USA
    J Infect Dis 193:703-12. 2006
    ..We conclude that an early Treg cell response during acute SIV infection may contribute to viral persistence by prematurely limiting the antiviral immune response before infection is cleared...
  80. ncbi request reprint DNA immunization in combination with effective antiretroviral drug therapy controls viral rebound and prevents simian AIDS after treatment is discontinued
    Deborah Heydenburg Fuller
    PowderJect Vaccines, Inc, Middleton, WI 53562, USA
    Virology 348:200-15. 2006
    ..Immunizing before infection or with multi-epitopes enhanced these effects. These results demonstrate that DNA immunization during antiretroviral therapy may be an effective strategy to treat HIV infection...
  81. ncbi request reprint HIV vaccine design: insights from live attenuated SIV vaccines
    Wayne C Koff
    International AIDS Vaccine Initiative, New York, New York 10038, USA
    Nat Immunol 7:19-23. 2006
    ..Here, the strategies defining key components of the protective immune response elicited by these vaccines are discussed...
  82. pmc Impact of MHC class I diversity on immune control of immunodeficiency virus replication
    Philip J R Goulder
    Department of Paediatrics, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK
    Nat Rev Immunol 8:619-30. 2008
    ..Here, we review recent studies of T-cell-mediated control of HIV and SIV infection, and offer insight for the design of a successful T-cell-based HIV vaccine in the future...
  83. doi request reprint HIV vaccine research: the way forward
    Anthony S Fauci
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892, USA
    Science 321:530-2. 2008
    ..This article summarizes progress and challenges in HIV vaccine research, the priorities arising from a recent summit at NIAID, and the actions needed, some already under way, to address those priorities...
  84. ncbi request reprint Within-host evolution of CD8+-TL epitopes encoded by overlapping and non-overlapping reading frames of simian immunodeficiency virus
    Austin L Hughes
    Department of Biological Sciences, University of South Carolina Columbia, SC 29208, USA
    Bioinformatics 21:iii39-44. 2005
    ....
  85. ncbi request reprint The role of the SIV model in AIDS vaccine research
    Thomas C Friedrich
    IAVI Rep 9:1, 6-8. 2005
  86. ncbi request reprint The pigtail macaque MHC class I allele Mane-A*10 presents an immundominant SIV Gag epitope: identification, tetramer development and implications of immune escape and reversion
    Miranda Z Smith
    Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic, Australia
    J Med Primatol 34:282-93. 2005
    ..Mane-A*10(+) animals have lower set point SIV levels than Mane-A*10(-) animals, suggesting a significant fitness cost of escape. These studies pave the way for a more robust understanding of HIV vaccines in pigtail macaques...
  87. pmc CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus: too late and too little
    Matthew R Reynolds
    Wisconsin Primate Research Center, University of Wisconsin, Madison 53715, USA
    J Virol 79:9228-35. 2005
    ....
  88. ncbi request reprint Rhesus macaque MHC class I molecules present HLA-B-like peptides
    Heather D Hickman-Miller
    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    J Immunol 175:367-75. 2005
    ..Therefore, endogenous peptide characterization indicates that macaque class I molecules may be the functional equivalents of HLA-B molecules...
  89. ncbi request reprint Induction of anti-simian immunodeficiency virus cellular and humoral immune responses in rhesus macaques by peptide immunogens: correlation of CTL activity and reduction of cell-associated but not plasma virus load following challenge
    Thorsten U Vogel
    Paul Ehrlich Institute, 63225 Langen, Germany
    J Gen Virol 83:81-91. 2002
    ..A significant inverse correlation between the levels of CTLp and the number of infected cells in circulation was observed. However, no such correlation with the plasma viral load (RNA copies/ml) was evident...

Research Grants51

  1. The Functional Significance of Cytotoxic T Lymphocyte Escape
    David Watkins; Fiscal Year: 2007
    ..Finally, we hypothesize that escaped virus evolving without any selective pressure on the "pre-escaped" CTL and HTL epitopes will evolve towards higher fitness viruses. ..
  2. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David I Watkins; Fiscal Year: 2010
    ..Furthermore, SIV challenge of vaccinated macaques is critical to HIV vaccine development. Understanding the MHC molecules of the macaque is central to both pathogenesis and vaccine studies. ..
  3. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2007
    ..II. Adapt technologies for HLA Typing to molecular typing of macaque (Indian rhesus, Chinese rhesus and Cynomolgus) class I and II. ..
  4. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2007
    ..The specifictetramer reagents, the binding assays and the MHC prediction tools will greatly expand our capacity to study immune responses. ..
  5. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2007
    ..In Specific Aim II we will carry out vaccine efficacy experiments to engender the most efficacious CD8+ responses against epitopes defined in Specific Aim I. ..
  6. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2006
    ..II. Adapt technologies for HLA Typing to molecular typing of macaque (Indian rhesus, Chinese rhesus and Cynomolgus) class I and II. ..
  7. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2006
    ..The specific tetramer reagents, the binding assays and the MHC prediction tools will greatly expand our capacity to study immune responses. ..
  8. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2006
    ..In Specific Aim II we will carry out vaccine efficacy experiments to engender the most efficacious CD8+ responses against epitopes defined in Specific Aim I. ..
  9. The Functional Significance of CTL Escape
    David Watkins; Fiscal Year: 2006
    ..Finally, we hypothesize that escaped virus evolving without any selective pressure on the "pre-escaped" CTL and HTL epitopes will evolve towards higher fitness viruses. ..
  10. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2005
    ..The specific tetramer reagents, the binding assays and the MHC prediction tools will greatly expand our capacity to study immune responses. ..
  11. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2005
    ..In Specific Aim II we will carry out vaccine efficacy experiments to engender the most efficacious CD8+ responses against epitopes defined in Specific Aim I. ..
  12. Minigene Vaccination with Early Presented Viral Proteins
    David Watkins; Fiscal Year: 2007
    ..We feel that this proposal represents a highly significant and innovative approach to address the HIV epidemic. ..
  13. Minigene Vaccination with Early Presented Viral Proteins
    David I Watkins; Fiscal Year: 2010
    ..We feel that this proposal represents a highly significant and innovative approach to address the HIV epidemic. ..
  14. MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES
    David I Watkins; Fiscal Year: 2010
    ..Identification of MHC alleles and definition of SIV-specific epitopes is critical in the definition of the immune response in this biomedically important system. ..
  15. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2009
    ..Furthermore, SIV challenge of vaccinated macaques is critical to HIV vaccine development. Understanding the MHC molecules of the macaque is central to both pathogenesis and vaccine studies. ..
  16. MHC-bound, SIV-derived, CTL & HTL Epitopes
    David Watkins; Fiscal Year: 2009
    ..The specifictetramer reagents, the binding assays and the MHC prediction tools will greatly expand our capacity to study immune responses. ..
  17. Minigene Vaccination with Early Presented Viral Proteins
    David Watkins; Fiscal Year: 2009
    ..We feel that this proposal represents a highly significant and innovative approach to address the HIV epidemic. ..
  18. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2009
    ..In Specific Aim II we will carry out vaccine efficacy experiments to engender the most efficacious CD8+ responses against epitopes defined in Specific Aim I. ..
  19. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2005
    ..II. Adapt technologies for HLA Typing to molecular typing of macaque (Indian rhesus, Chinese rhesus and Cynomolgus) class I and II. ..
  20. The Functional Significance of CTL Escape
    David Watkins; Fiscal Year: 2005
    ..Finally, we hypothesize that escaped virus evolving without any selective pressure on the "pre-escaped" CTL and HTL epitopes will evolve towards higher fitness viruses. ..
  21. A Novel Chlamydial Vector for HIV Vaccine Development
    David Watkins; Fiscal Year: 2005
    ..However, the immediate goal of this limited R21 application is to explore the innovative idea of using Chlamydia as a vaccine vector. ..
  22. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2002
    ..One of these laboratories will be at the WRPRC under the direction of Dr. David Watkins and the other will be located at the Biomedical Primate Research Center (the Netherlands) under the direction ..
  23. MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES
    David Watkins; Fiscal Year: 2001
    ..Definition of new MHC/peptide combinations and the production of MHC-defined animals has been a priority of the Baltimore AVRC Committee (see letter of support from Dr. Baltimore; Appendix). ..
  24. STUDY OF MHC & CTL IN OPIATE-DEPENDENT MONKEYS WITH AIDS
    David Watkins; Fiscal Year: 2001
    ..In this cohort of animals they will be able to determine whether opiates can influence the cellular immune response to the AIDS virus. ..
  25. CTL-BASED VACCINES FOR THE AIDS VIRUS
    David Watkins; Fiscal Year: 2001
    ..John Altman will synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will immunize animals using the gene gun. ..
  26. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2001
    ..One of these laboratories will be at the WRPRC under the direction of Dr. David Watkins and the other will be located at the Biomedical Primate Research Center (the Netherlands) under the direction ..
  27. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2001
    ..Indeed, a CTL epitope-based vaccine is already in Phase I trials in Oxford and Kenya under the direction of Dr. McMichael. Thus, results from our studies will be important in the eventual design of this vaccine. ..
  28. STUDY OF MHC & CTL IN OPIATE DEPENDENT MONKEYS WITH AIDS
    David Watkins; Fiscal Year: 2000
    ..In this cohort of animals they will be able to determine whether opiates can influence the cellular immune response to the AIDS virus. ..
  29. STUDY OF MHC & CTL IN OPIATE-DEPENDENT MONKEYS WITH AIDS
    David Watkins; Fiscal Year: 2000
    ..In this cohort of animals they will be able to determine whether opiates can influence the cellular immune response to the AIDS virus. ..
  30. CTL-BASED VACCINES FOR THE AIDS VIRUS
    David Watkins; Fiscal Year: 2000
    ..John Altman will synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will immunize animals using the gene gun. ..
  31. CTL-BASED VACCINES FOR THE AIDS VIRUS
    David Watkins; Fiscal Year: 1999
    ..John Altman will synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will immunize animals using the gene gun. ..
  32. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2002
    ..Indeed, a CTL epitope-based vaccine is already in Phase I trials in Oxford and Kenya under the direction of Dr. McMichael. Thus, results from our studies will be important in the eventual design of this vaccine. ..
  33. STUDY OF MHC & CTL IN OPIATE-DEPENDENT MONKEYS WITH AIDS
    David Watkins; Fiscal Year: 2002
    ..In this cohort of animals they will be able to determine whether opiates can influence the cellular immune response to the AIDS virus. ..
  34. CTL-BASED VACCINES FOR THE AIDS VIRUS
    David Watkins; Fiscal Year: 2002
    ..John Altman will synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will immunize animals using the gene gun. ..
  35. MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES
    David Watkins; Fiscal Year: 2004
    ..Definition of new MHC/peptide combinations and the production of MHC-defined animals has been a priority of the Baltimore AVRC Committee (see letter of support from Dr. Baltimore; Appendix). ..
  36. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2004
    ..II. Adapt technologies for HLA Typing to molecular typing of macaque (Indian rhesus, Chinese rhesus and Cynomolgus) class I and II. ..
  37. The Functional Significance of CTL Escape
    David Watkins; Fiscal Year: 2004
    ..Finally, we hypothesize that escaped virus evolving without any selective pressure on the "pre-escaped" CTL and HTL epitopes will evolve towards higher fitness viruses. ..
  38. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2004
    ..Indeed, a CTL epitope-based vaccine is already in Phase I trials in Oxford and Kenya under the direction of Dr. McMichael. Thus, results from our studies will be important in the eventual design of this vaccine. ..
  39. The Functional Significance of CTL Escape
    David Watkins; Fiscal Year: 2003
    ..Finally, we hypothesize that escaped virus evolving without any selective pressure on the "pre-escaped" CTL and HTL epitopes will evolve towards higher fitness viruses. ..
  40. CTL-BASED VACCINES FOR THE AIDS VIRUS
    David Watkins; Fiscal Year: 2003
    ..John Altman will synthesize MHC class I tetramers for CTL quantitation and Deborah Fuller will immunize animals using the gene gun. ..
  41. MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES
    David Watkins; Fiscal Year: 2003
    ..Definition of new MHC/peptide combinations and the production of MHC-defined animals has been a priority of the Baltimore AVRC Committee (see letter of support from Dr. Baltimore; Appendix). ..
  42. A NOVEL, LOGICAL APPROACH TO HIV VACCINE DEVELOPMENT
    David Watkins; Fiscal Year: 2003
    ..Indeed, a CTL epitope-based vaccine is already in Phase I trials in Oxford and Kenya under the direction of Dr. McMichael. Thus, results from our studies will be important in the eventual design of this vaccine. ..
  43. MHC TYPING OF MACAQUES USED IN AIDS RESEARCH
    David Watkins; Fiscal Year: 2003
    ..One of these laboratories will be at the WRPRC under the direction of Dr. David Watkins and the other will be located at the Biomedical Primate Research Center (the Netherlands) under the direction ..
  44. MHC-BOUND, SIV-DERIVED, CTL AND HTL EPITOPES
    David Watkins; Fiscal Year: 2002
    ..Definition of new MHC/peptide combinations and the production of MHC-defined animals has been a priority of the Baltimore AVRC Committee (see letter of support from Dr. Baltimore; Appendix). ..
  45. STUDY OF MHC & CTL IN OPIATE DEPENDENT MONKEYS WITH AIDS
    David Watkins; Fiscal Year: 1999
    ..In this cohort of animals they will be able to determine whether opiates can influence the cellular immune response to the AIDS virus. ..