Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8<sup>+</sup>and CD4<sup>+</sup>T-Cell Responses from Chronically Infected Individuals

Engelmayer, Jose; Larsson, Marie; Lee, Andrew; Lee, Marina; Cox, William I.; Steinman, Ralph M.; Bhardwaj, Nina

doi:10.1128/jvi.75.5.2142-2153.2001

Cited by 75 publications

(48 citation statements)

References 62 publications

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“…It has been reported that DC function, particularly chemotaxis and susceptibility to apoptosis, may be deranged in the context of HIV infection (28,29). However, pox virus-activated DCs can elicit CD4 and CD8 responses in chronically HIV-infected individuals (30). Thus, targeting DCs ex vivo or in vivo with peptide or a DNA vaccine approach with CD40L as an adjuvant may ultimately induce therapeutic vaccine responses in high-risk individuals.…”

Section: Discussionmentioning

confidence: 99%

CD4+ T cell–independent vaccination against Pneumocystis carinii in mice

Zheng¹,

Shellito²,

Marrero³

et al. 2001

J. Clin. Invest.

100

104

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Section: Discussionmentioning

confidence: 99%

CD4+ T cell–independent vaccination against Pneumocystis carinii in mice

Zheng¹,

Shellito²,

Marrero³

et al. 2001

J. Clin. Invest.

100

104

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“…The infection is abortive, with only early viral gene products being expressed; and when immature DCs are infected, infection is followed by either overt cytotoxicity 154 or a block in maturation. 155 Nevertheless, efficient presentation of the recombinant gene is observed in culture, 154,156 possibly through cross-presentation of dying infected DCs by other noninfected DCs. 157,158 Even UVinactivated, recombinant vaccinia is presented on MHC class I products of DCs.…”

Section: Viral Vectorsmentioning

confidence: 99%

Active immunization against cancer with dendritic cells: The near future

2001

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DCs 1 are antigen-presenting cells that regulate several components of the immune system. The mature or terminal stage of DC development induces specific T-cell immunity and resistance to experimental tumors in vivo. However, DC maturation is induced by inflammatory and microbial stimuli, so it is unlikely that mature DCs normally present antigens from tumor cells in cancer patients. Accordingly, clinical studies have begun in which DCs are generated ex vivo, charged with tumor antigens, exposed to maturation stimuli and reinfused to immunize patients. This approach has the potential to control responses to cancer antigens in a specific and nontoxic manner, in both vaccination and therapeutic settings.DCs can mobilize several immune resistance mechanisms. These include CD8ϩ CTLs, CD4 ϩ helper T cells, NK and NKT cells. Each of these lymphocytes recognizes targets through a distinct mechanism and has the capacity to kill tumor cells and release valuable protective cytokines like IFN-␥. CD4 ϩ T cells also provide essential help for the expansion and maintenance of CD8 ϩ cytolytic cells, while NK and NKT cells can eliminate targets that dampen presentation on MHC class I to escape CTL recognition. The stimulation and concerted action of these classes of lymphocytes can now be studied directly in patients, using ex vivo-derived DCs.Several findings have emerged from studies of healthy volunteers who have been immunized with DCs charged with model antigens, KLH protein and influenza virus matrix peptide. Mature DCs elicit a polarized Th1 type of CD4 T-cell response, only a single injection being required. Vaccination with antigen-bearing DCs also markedly improves the functional affinity of CD8 ϩ T cells. These findings are important in the context of immunotherapy because Th1 cells are more efficient helper cells in experimental models of viral infection and tumors, while high-affinity CTLs should improve recognition of tumor-derived peptides. An important caution also has surfaced when DCs are not adequately differentiated. Immature DCs can silence adaptive T-cell responses, e.g., by inducing IL-10 -producing, T-reg cells.DC-based active immunization does not result in major shortterm toxicity in healthy subjects or cancer patients. Tumor-specific T-cell responses have been induced and detected in fresh blood specimens without the need for restimulation in vitro. However, the immune responses observed in the first protocols are still smaller than those seen naturally in acute viral infections. Occasional clinical regressions have been noted in these initial feasibility studies, particularly in melanomas, pediatric tumors, lymphomas, prostate cancers and renal cell cancers. This information, coupled with progress in DC biology, suggests many ways to improve the efficacy of this new therapy. Some relevant topics include antigen loading and DC maturation procedures, frequency and route of DC injection, efficiency of DC homing to lymphoid tissues and their longevity once there and the role of distinct DC subsets. A val...

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“…CNPV-based vaccines have proven effective in prime-boost vaccine strategies and as immunoadjuvants through expression of recombinant cytokines and costimulatory proteins (47,(67)(68)(69)90). Recent evidence suggests that dendritic cell antigen presentation, maturation, and apoptosis are important in CNPV-generated immunity (24,41,55,59). Improved understanding of virus-host interactions should yield improved vaccine vectors, as demonstrated by recent incorporation of vaccinia virus (VACV) host response modification genes to create a third-generation CNPV-based vaccine (28,44).…”

mentioning

confidence: 99%

The Genome of Canarypox Virus

Tulman

Afonso

et al. 2004

J Virol

174

206

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Here we present the genomic sequence, with analysis, of a canarypox virus (CNPV). The 365-kbp CNPV genome contains 328 potential genes in a central region and in 6.5-kbp inverted terminal repeats. Comparison with the previously characterized fowlpox virus (FWPV) genome revealed avipoxvirus-specific genomic features, including large genomic rearrangements relative to other chordopoxviruses and novel cellular homologues and gene families. CNPV also contains many genomic differences with FWPV, including over 75 kbp of additional sequence, 39 genes lacking FWPV homologues, and an average of 47% amino acid divergence between homologues. Differences occur primarily in terminal and, notably, localized internal genomic regions and suggest significant genomic diversity among avipoxviruses. Divergent regions contain gene families, which overall comprise over 49% of the CNPV genome and include genes encoding 51 proteins containing ankyrin repeats, 26 N1R/p28-like proteins, and potential immunomodulatory proteins, including those similar to transforming growth factor ␤ and ␤-nerve growth factor. CNPV genes lacking homologues in FWPV encode proteins similar to ubiquitin, interleukin-10-like proteins, tumor necrosis factor receptor, PIR1 RNA phosphatase, thioredoxin binding protein, MyD116 domain proteins, circovirus Rep proteins, and the nucleotide metabolism proteins thymidylate kinase and ribonucleotide reductase small subunit. These data reveal genomic differences likely affecting differences in avipoxvirus virulence and host range, and they will likely be useful for the design of improved vaccine vectors.Within the Chordopoxvirinae subfamily (poxviruses of vertebrates) of the Poxviridae, Avipoxvirus is the only characterized genus to infect nonmammalian hosts (57, 60), including more than 60 species of wild birds representing 20 families (60, 97). Variable restriction enzyme profiles suggest significant genomic differences among avipoxviruses (32,97,98). Crossinfection studies also suggest genetic differences among avipoxviruses, as specific virus-host combinations may not be cross-protective and result in a wide range of pathogenic effects, from absence of clinical disease to generalized infection and death (8,97).Canarypox virus (CNPV) is an avipoxvirus and etiologic agent of canarypox, a disease of birds both in the wild and in commercial aviaries, where significant losses result (15,16,33,45). Canarypox has been described broadly as the poxviral disease of passeriform (song) birds, efficiently causing disease in passerine hosts compared to galliform (domestic fowl) and columbiform (pigeon) hosts (8,15,22,33). However, passerine host preferences exist, and current International Committee on Taxonomy of Viruses classification differentiates between CNPV and several other passerine isolates (60, 97). CNPV produces clinical signs similar to generalized poxviral infections of other birds, including both cutaneous and diptheretic disease forms caused by the prototypical galliform avipoxvirus, fowlpox virus (FWPV), and incl...

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Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8⁺and CD4⁺T-Cell Responses from Chronically Infected Individuals

Cited by 75 publications

References 62 publications

CD4+ T cell–independent vaccination against Pneumocystis carinii in mice

CD4+ T cell–independent vaccination against Pneumocystis carinii in mice

Active immunization against cancer with dendritic cells: The near future

The Genome of Canarypox Virus

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Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8+and CD4+T-Cell Responses from Chronically Infected Individuals

Cited by 75 publications

References 62 publications

CD4+ T cell–independent vaccination against Pneumocystis carinii in mice

CD4+ T cell–independent vaccination against Pneumocystis carinii in mice

Active immunization against cancer with dendritic cells: The near future

The Genome of Canarypox Virus

Contact Info

Product

Resources

About

Mature Dendritic Cells Infected with Canarypox Virus Elicit Strong Anti-Human Immunodeficiency Virus CD8⁺and CD4⁺T-Cell Responses from Chronically Infected Individuals