Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccinationD H Barouch
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
Science 290:486-92. 2000
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- Viral evolution and challenges in the development of HIV vaccines
Dan H Barouch
Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Research East Room 113, Boston, MA 02215, USA
Vaccine 20:A66-8. 2002
..These data suggest that viral escape from CTL may prove to be a significant limitation of the current generation of CTL-based AIDS vaccines...
- BK virus-associated hemorrhagic cystitis in a Human Immunodeficiency Virus-infected patient
Dan H Barouch
Division of Infectious Diseases, Massachusetts General Hospital, and Division of Infectious Diseases, Brigham and Women s Hospital, Boston, MA, USA
Clin Infect Dis 35:326-9. 2002
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- 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...
- 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...
- Vaccine-elicited immune responses prevent clinical AIDS in SHIV(89.6P)-infected rhesus monkeys
D H Barouch
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
Immunol Lett 79:57-61. 2001
..Vaccine approaches that elicit immune responses capable of reducing plasma viral loads, but not capable of inducing sterilizing immunity, may still provide substantial clinical benefits...
- CD8+ cytotoxic T lymphocyte responses to lentiviruses and herpesviruses
D H Barouch
Harvard Medical School and Beth Israel Deaconess Medical Center, Research East 113, 330 Brookline Avenue, Boston, MA 02215, USA
Curr Opin Immunol 13:479-82. 2001
..These findings underscore the importance of CD8+ CTLs in the immune control of persistent viral infections...
Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys by recombinant modified vaccinia virus Ankara vaccinationD H Barouch
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 75:5151-8. 2001
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- Elicitation of high-frequency cytotoxic T-lymphocyte responses against both dominant and subdominant simian-human immunodeficiency virus epitopes by DNA vaccination of rhesus monkeys
D H Barouch
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 75:2462-7. 2001
..These data demonstrate that plasmid DNA may be useful in eliciting a broad CTL response against multiple epitopes...
- Functional equivalency of B7-1 and B7-2 for costimulating plasmid DNA vaccine-elicited CTL responses
S Santra
Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Immunol 165:6791-5. 2000
..Functional differences between B7-1 and B7-2 observed in vivo therefore may not reflect inherent differences in the interactions of CD28 with these ligands...
- Translational Mini-Review Series on Vaccines for HIV: Harnessing innate immunity for HIV vaccine development
E G Rhee
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Clin Exp Immunol 157:174-80. 2009
..Here, we review recent advances in innate immunity, focusing upon their potential applications in developing adjuvants and vectors for HIV vaccines...
- Translational Mini-Review Series on Vaccines for HIV: T lymphocyte trafficking and vaccine-elicited mucosal immunity
D R Kaufman
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
Clin Exp Immunol 157:165-73. 2009
..Increasing the synergy between these avenues of research may afford new opportunities for mucosal vaccine design...
- 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...
- Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-ad5 immunity
Angelique A C Lemckert
Crucell Holland B. V, Leiden, The Netherlands
J Virol 79:9694-701. 2005
..Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes...
- 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...
- 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...
- 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...
- Adenovirus vector-based vaccines for human immunodeficiency virus type 1
Dan H Barouch
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Hum Gene Ther 16:149-56. 2005
..In this review, we describe progress in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1...
- 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
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- Immunogenicity of recombinant fiber-chimeric adenovirus serotype 35 vector-based vaccines in mice and rhesus monkeys
Anjali Nanda
Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
J Virol 79:14161-8. 2005
..Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes...
- Rational design of gene-based vaccines
Dan H Barouch
Research East Room 113, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
J Pathol 208:283-9. 2006
..In this review, current strategies to develop and optimize gene-based vaccines are described, with an emphasis on novel approaches to improve plasmid DNA vaccines and recombinant adenovirus vector-based vaccines...
- Modulation of DNA vaccine-elicited CD8+ T-lymphocyte epitope immunodominance hierarchies
Jinyan Liu
Research East Room 213, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
J Virol 80:11991-7. 2006
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- Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys
Jinyan Liu
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Virol 82:4844-52. 2008
..Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens...
- Recruitment of antigen-presenting cells to the site of inoculation and augmentation of human immunodeficiency virus type 1 DNA vaccine immunogenicity by in vivo electroporation
Jinyan Liu
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 82:5643-9. 2008
..Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy...
- HIV-1 vaccine candidate ineffective
Dan H Barouch
AIDS Clin Care 19:93. 2007
- 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...
- Trafficking of antigen-specific CD8+ T lymphocytes to mucosal surfaces following intramuscular vaccination
David R Kaufman
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Immunol 181:4188-98. 2008
..Thus, i.m. vaccination can overcome immune compartmentalization and generate robust mucosal CD8(+) T lymphocyte memory. These data demonstrate that the systemic and mucosal immune systems are highly coordinated following vaccination...
- Challenges in the development of an HIV-1 vaccine
Dan H Barouch
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 455:613-9. 2008
..Here I review key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine...
- 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
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- 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
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- Simian-human immunodeficiency virus escape from cytotoxic T-lymphocyte recognition at a structurally constrained epitope
Fred W Peyerl
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
J Virol 77:12572-8. 2003
..Together, these data suggest that a compensatory mutation is selected for in SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope...
- 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...
- Magnitude and diversity of cytotoxic-T-lymphocyte responses elicited by multiepitope DNA vaccination in rhesus monkeys
Ramu A Subbramanian
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Research East-RE 113, 330 Brookline Avenue, Boston, MA 02215, USA
J Virol 77:10113-8. 2003
..These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance...
- 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...
- 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...
- 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...
- 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...
- DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate
Mary Premenko-Lanier
California National Primate Research Center and Department of Pathology, School of Medicine, University of California-Davis, County Road 98, Davis, CA 95616-8542, USA
Virology 307:67-75. 2003
..Further, the addition of a molecular IL-2 adjuvant augments this DNA vaccine...
- 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...
- Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4+ and CD8+ T lymphocyte responses
Paul F McKay
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02215, USA
Eur J Immunol 34:1011-20. 2004
..Moreover, these studies show that different subsets of professional APC can selectively modulate DNA vaccine-elicited T lymphocyte responses...
- 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...
- Challenges in the search for an HIV vaccine
Angelique A C Lemckert
Crucell Holland BV, 2301 CA Leiden, The Netherlands
Eur J Epidemiol 19:513-6. 2004
..An immunogen that elicits broadly reactive neutralizing antibodies, however, has yet to be developed...
- 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
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- Structural constraints on viral escape from HIV- and SIV-specific cytotoxic T-lymphocytes
Fred W Peyerl
Division of Viral Pathogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Viral Immunol 17:144-51. 2004
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- 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...
- 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...
- 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
- 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...
- HIV vaccine trial canceled
Dan H Barouch
AIDS Clin Care 20:69. 2008
- The role of cytokine DNAs as vaccine adjuvants for optimizing cellular immune responses
Dan H Barouch
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA, USA
Immunol Rev 202:266-74. 2004
..Here, we review recent advances in our understanding of cytokine biology, T-lymphocyte differentiation, and potential applications of plasmid cytokines in the rational design of improved vaccines...
- Differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice
David R Kaufman
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Virol 82:6829-37. 2008
..These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines...
- Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D
Peter Abbink
Research East Room 213, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
J Virol 81:4654-63. 2007
..These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world...
- Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity
Anna R Thorner
Research East Room 213, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
J Virol 80:12009-16. 2006
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- Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: manufacture on PER.C6 cells, tropism and immunogenicity
Angelique A C Lemckert
Crucell Holland BV, PO Box 2048, 2301 CA Leiden, The Netherlands
J Gen Virol 87:2891-9. 2006
..SIVGag vaccine. These data demonstrate the potential of a replication deficient human group D adenoviral vector for vaccination purposes...
- Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein
Shawn M Sumida
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
J Immunol 174:7179-85. 2005
..These studies suggest a potential strategy for engineering novel Ad5 vectors to evade dominant Ad5-specific NAbs...
- Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity
Diane M Roberts
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Nature 441:239-43. 2006
..Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy...
