Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosaIgor M Belyakov
Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA
Blood 107:3258-64. 2006
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Generation of functionally active HIV-1 specific CD8+ CTL in intestinal mucosa following mucosal, systemic or mixed prime-boost immunizationIgor M Belyakov
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA Midwest Research Institute, Frederick, MD 21702, USA
Virology 381:106-15. 2008
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- What role does the route of immunization play in the generation of protective immunity against mucosal pathogens?
Igor M Belyakov
Midwest Research Institute, 110 Thomas Johnson Drive, Frederick, MD 21702, USA
J Immunol 183:6883-92. 2009
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- Mucosal immunity and HIV-1 infection: applications for mucosal AIDS vaccine development
Igor M Belyakov
Midwest Research Institute, 110 Thomas Johnson Drive, Suite 170 Frederick, MD 21702, USA
Curr Top Microbiol Immunol 354:157-79. 2012
..Moreover, we propose immunization strategies that may be able to elicit an effective immune response that can protect against AIDS as well as other mucosal infections...
Role of alpha3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLsIgor M Belyakov
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Int Immunol 19:1413-20. 2007
..Thus, low-avidity CTL may not be able to take advantage of the interaction between CD8 and the alpha3 domain of non-presenting class I MHC molecules, perhaps because of a shorter dwell time for the TCR-MHC interaction...
- A novel functional CTL avidity/activity compartmentalization to the site of mucosal immunization contributes to protection of macaques against simian/human immunodeficiency viral depletion of mucosal CD4+ T cells
Igor M Belyakov
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 178:7211-21. 2007
..This preferential localization of high-avidity CTL may explain previous differences in vaccination results and may guide future vaccination strategy...
- Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines
I M Belyakov
Department of Internal Medicine, and Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, School of Medicine, Ann Arbor, Michigan 48109, USA
Curr Med Chem 18:3953-62. 2011
..Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection...
- Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques
Yongjun Sui
Vaccine Branch, Biostatistics and Data Management Section, and Laboratory of Experimental Immunology, National Cancer Institute, and Laboratory of Host Defenses and Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 107:9843-8. 2010
..Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity...
- Avidity of CD8 T cells sharpens immunodominance
Amiran H Dzutsev
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1578, USA
Int Immunol 19:497-507. 2007
..Since most self-reactive T cells of high avidity are depleted in the thymus, the selection of immunodominant epitopes based on the expansion of high-avidity T cells in the periphery reduces the potential for autoimmunity...
- Enhancement of CD8+ T cell immunity in the lung by CpG oligodeoxynucleotides increases protective efficacy of a modified vaccinia Ankara vaccine against lethal poxvirus infection even in a CD4-deficient host
Igor M Belyakov
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 177:6336-43. 2006
..This study demonstrates for the first time a protective adjuvant effect of CpG ODN for a live viral vector vaccine that may overcome CD4 deficiency in the induction of protective CD8(+) T cell-mediated immunity...
- Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques
Yvette Edghill-Smith
Laboratory of Receptor Biology and Gene Expression, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-5055, USA
J Infect Dis 188:1181-91. 2003
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- Estimation of low frequency antigen-presenting cells with a novel RELISPOT assay
Amiran K Dzutsev
Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892 1578, USA
J Immunol Methods 333:71-8. 2008
..Using this RELISPOT (Rosette ELISPOT) method we demonstrate the dynamic interplay between CD8 T cells and professional and non-professional APCs following virus challenge...
- Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA
Linda S Wyatt
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Virology 372:260-72. 2008
..Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines...
- Memories that last forever: strategies for optimizing vaccine T-cell memory
Jeffrey D Ahlers
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
Blood 115:1678-89. 2010
..In this review we will focus on discussing mechanisms involved in T-cell memory and provide promising new approaches toward expanding current vaccine strategies to enhance antiviral memory...
- Protection against lethal vaccinia virus challenge in HLA-A2 transgenic mice by immunization with a single CD8+ T-cell peptide epitope of vaccinia and variola viruses
James T Snyder
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA
J Virol 78:7052-60. 2004
..1-positive individuals, representing almost half the population...
- TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4⁺ memory T cell loss in SIVmac251-challenged rhesus macaques
Yongjun Sui
Vaccine Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, United States
Vaccine 30:59-68. 2011
..Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4(+) T cell levels and SIV viral load...
- Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses
Igor M Belyakov
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 100:9458-63. 2003
..These properties, shared with the existing smallpox vaccine, provide a basis for further evaluation of these replication-deficient vaccinia viruses as safer vaccines against smallpox or against complications from vaccinia virus...
- The IL-15 receptor {alpha} chain cytoplasmic domain is critical for normal IL-15Ralpha function but is not required for trans-presentation
Zheng Wu
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
Blood 112:4411-9. 2008
..These experiments collectively indicate that IL-15Ralpha can act in cis in addition to acting in trans to present IL-15 to responding cells...
- The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response
Alexander Kotelkin
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 8007, USA
J Virol 80:5958-67. 2006
..Thus, the NS2 protein of HRSV suppresses the CTL component of the adaptive immune response, and this appears to be a consequence of its suppression of type I IFN...
- Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice
Qing Zhu
Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 120:607-16. 2010
..Therefore, selective TLR ligand combinations can increase protective efficacy by increasing the quality rather than the quantity of T cell responses...
- Expression of interleukin-4 by recombinant respiratory syncytial virus is associated with accelerated inflammation and a nonfunctional cytotoxic T-lymphocyte response following primary infection but not following challenge with wild-type virus
Alexander Bukreyev
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Cancer Institute, Bethesda, MD 20892 8007, USA
J Virol 79:9515-26. 2005
..Thus, a strong Th2 environment during primary pulmonary immunization with live RSV resulted in early inflammation and a largely nonfunctional primary CTL response but had a minimal effect on the secondary response...
- Transcutaneous immunization induces mucosal CTLs and protective immunity by migration of primed skin dendritic cells
Igor M Belyakov
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1578, USA
J Clin Invest 113:998-1007. 2004
..These results and previous clinical trial results support the observation that TCI is a safe and effective strategy for inducing strong mucosal antibody and CTL responses...
- New paradigms for generating effective CD8+ T cell responses against HIV-1/AIDS
Jeffrey D Ahlers
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20817, USA
Discov Med 9:528-37. 2010
..Here, we highlight factors considered essential for effective HIV-1 vaccine CD8+ T cell responses: vaccine antigens, quality, magnitude and breadth, mucosal targeting, and formation of CD8+ T cell mucosal memory...
- Immunobiology of mucosal HIV infection and the basis for development of a new generation of mucosal AIDS vaccines
Igor M Belyakov
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Immunity 20:247-53. 2004
..Recent understanding of mucosal HIV transmission and of chemokines and integrins in mucosal trafficking can aid design of new strategies to enhance AIDS vaccine efficacy...
- Cytokine, chemokine, and costimulatory molecule modulation to enhance efficacy of HIV vaccines
Jeffrey D Ahlers
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA
Curr Mol Med 3:285-301. 2003
..In this review we will discuss the application and delivery of cytokines, costimulatory molecules, and chemokines toward improving current vaccine strategies...
- Strategies for optimizing targeting and delivery of mucosal HIV vaccines
Jeffrey D Ahlers
Division of AIDS, NIAID, NIH, Rockville, MD 20817, USA
Eur J Immunol 39:2657-69. 2009
..Here, we discuss novel vaccine strategies and adjuvants for optimizing mucosal delivery of HIV vaccines...
- Progress on new vaccine strategies against chronic viral infections
Jay A Berzofsky
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, The Center for Cancer Research, National Cancer Institute NIH, 10 Center Drive, Bethesda, MD 20892, USA
J Clin Invest 114:450-62. 2004
..We also explore novel strategies for increasing the immunogenicity and efficacy of vaccines...
- Lack of IL-7 and IL-15 signaling affects interferon-γ production by, more than survival of, small intestinal intraepithelial memory CD8+ T cells
Dmitry Isakov
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Eur J Immunol 41:3513-28. 2011
..Taken together, these results reveal that survival factors, as well as the functional activity, of antigen-specific CD8(+) T cells in the SI-IEL compartments may markedly differ from their counterparts in peripheral lymphoid tissues...
- A push-pull approach to maximize vaccine efficacy: abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L
Jeffrey D Ahlers
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 99:13020-5. 2002
..These results argue for a push-pull approach to maximize vaccine efficacy, especially for HIV and cancer...
- Functional CD8+ CTLs in mucosal sites and HIV infection: moving forward toward a mucosal AIDS vaccine
Igor M Belyakov
Midwest Research Institute, Frederick, MD 21702, USA
Trends Immunol 29:574-85. 2008
..e. the gastrointestinal and vaginal mucosae). Here we examine the current information regarding the role of mucosal immunity in prevention of HIV transmission and discuss strategies for mucosal AIDS vaccine development...
- Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines
Qing Zhu
Vaccine Branch, Center for Cancer Research, and Laboratory of Experimental Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 105:16260-5. 2008
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- Strategies for recruiting and targeting dendritic cells for optimizing HIV vaccines
Jeffrey D Ahlers
Division of AIDS, NIAID, National Institutes of Health, 6700 Rockledge Dr, Bethesda, MD 20817, USA
Trends Mol Med 15:263-74. 2009
..Here, we discuss current vaccine strategies for optimizing the induction of immune responses by the recruitment of DCs and the targeting of vaccine antigens to DCs...
- Progress on new vaccine strategies for the immunotherapy and prevention of cancer
Jay A Berzofsky
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 113:1515-25. 2004
..This review examines the fundamental immunologic advances and the novel vaccine strategies arising from these advances, as well as the early clinical trials studying new approaches to treat or prevent cancer...
- Mucosal AIDS vaccines: current status and future directions
Igor M Belyakov
Molecular Immunogenetics and Vaccine Research, Section, Vaccine Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA
Expert Rev Vaccines 3:S65-73. 2004
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- DNA vaccines encoding human immunodeficiency virus-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses
Arya Biragyn
Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Blood 100:1153-9. 2002
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- Molecular mechanisms and biological significance of CTL avidity
James T Snyder
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Curr HIV Res 1:287-94. 2003
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- Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking
Paul E Makidon
Division of Allergy and Clinical Immunology, Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
Eur J Immunol 42:2073-86. 2012
..This is the first observation of a nasal adjuvant that activates calreticulin-associated apoptosis of ciliated nasal epithelial cells to generate broad cytokine/chemokine responses in mucosal tissue...
- Molecular pathways regulating CD4(+) T cell differentiation, anergy and memory with implications for vaccines
Jeffrey D Ahlers
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20817, USA
Trends Mol Med 16:478-91. 2010
..Here, we discuss lineage instructive programs that regulate CD4(+) T cell differentiation and memory and how to translate this knowledge into vaccines and immunotherapies that promote protective immune responses...
- Lessons learned from natural infection: focusing on the design of protective T cell vaccines for HIV/AIDS
Jeffrey D Ahlers
NIAID, NIH, Bethesda, MD 20817, USA
Trends Immunol 31:120-30. 2010
..Here, we discuss qualitative parameters of the CD8(+) CTL response and mechanisms operative in the control of persistent virus infections and suggest new strategies for design and delivery of HIV vaccines...
- Cytokines in the thymus: production and biological effects
Alexandr A Yarilin
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Curr Med Chem 11:447-64. 2004
..The functions of many cytokines in the thymus are not established up to now. Detailed analysis of the "minor cytokine network" and intrathymic cytokine effects will reveal some unknown events of thymus physiology...
- Expression of immunomodulating molecules by recombinant viruses: can the immunogenicity of live virus vaccines be improved?
Alexander Bukreyev
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 8007, USA
Expert Rev Vaccines 1:233-45. 2002
..For this type of vaccine, expression of tumor antigens and one or more immunomodulating molecules by one or several recombinant viruses has been proposed...
- Fixation and cryopreservation of whole blood and isolated mononuclear cells: Influence of different procedures on lymphocyte subset analysis by flow cytometry
Ligia A Pinto
NCI Frederick SAIC Frederick, Frederick, Maryland, USA
Cytometry B Clin Cytom 63:47-55. 2005
..The development of methods that would allow preservation of samples for flow cytometric analysis is important for the extension of this technology to field testing in settings where the equipment might be not readily accessible...
- 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...
- Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4+ T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels
Ranajit Pal
Advanced BioScience Laboratories, Inc, Kensington, Maryland 20895, USA
J Virol 80:3732-42. 2006
..Thus, systemic immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune responses able to contain virus replication also at mucosal sites in macaques...
- Late effects of the Chernobyl radiation accident on T cell-mediated immunity in cleanup workers
Oleg Kuzmenok
Laboratory on Thymus Research, Department of Immunology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Av. Brasil, 4365-Manguinhos 21045-900 Brazil
Radiat Res 159:109-16. 2003
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