Abstract:
:This study describes a method for increasing the immunogenicity of influenza virus vaccines by exploiting the natural anti-Gal antibody to effectively target vaccines to antigen-presenting cells (APC). This method is based on enzymatic engineering of carbohydrate chains on virus envelope hemagglutinin to carry the alpha-Gal epitope (Gal alpha 1-3Gal beta 1-4GlcNAc-R). This epitope interacts with anti-Gal, the most abundant antibody in humans (1% of immunoglobulins). Influenza virus vaccine expressing alpha-Gal epitopes is opsonized in situ by anti-Gal immunoglobulin G. The Fc portion of opsonizing anti-Gal interacts with Fc gamma receptors on APC and induces effective uptake of the vaccine virus by APC. APC internalizes the opsonized virus to transport it to draining lymph nodes for stimulation of influenza virus-specific T cells, thereby eliciting a protective immune response. The efficacy of such an influenza vaccine was demonstrated in alpha 1,3galactosyltransferase (alpha 1,3GT) knockout mice, which produce anti-Gal, using the influenza virus strain A/Puerto Rico/8/34-H1N1 (PR8). Synthesis of alpha-Gal epitopes on carbohydrate chains of PR8 virus (PR8(alpha gal)) was catalyzed by recombinant alpha1,3GT, the glycosylation enzyme that synthesizes alpha-Gal epitopes in cells of nonprimate mammals. Mice immunized with PR8(alpha gal) displayed much higher numbers of PR8-specific CD8(+) and CD4(+) T cells (determined by intracellular cytokine staining and enzyme-linked immunospot assay) and produced anti-PR8 antibodies with much higher titers than mice immunized with PR8 lacking alpha-Gal epitopes. Mice immunized with PR8(alpha gal) also displayed a much higher level of protection than PR8 immunized mice after being challenged with lethal doses of live PR8 virus. We suggest that a similar method for increasing immunogenicity may be applicable to avian influenza vaccines.
journal_name
J Viroljournal_title
Journal of virologyauthors
Abdel-Motal UM,Guay HM,Wigglesworth K,Welsh RM,Galili Udoi
10.1128/JVI.00647-07subject
Has Abstractpub_date
2007-09-01 00:00:00pages
9131-41issue
17eissn
0022-538Xissn
1098-5514pii
JVI.00647-07journal_volume
81pub_type
杂志文章abstract::During latent herpes simplex virus type 1 (HSV-1) infection in the trigeminal ganglia of mice, three virus-specific transcripts, 2.0, 1.5, and 1.45 kilobases (kb), are detectable by Northern (RNA) blot analysis, but only the 2.0-kb transcript can be detected in HSV-1-infected tissue culture cells (J.G. Spivack and N. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3281-3287.1988
更新日期:1988-09-01 00:00:00
abstract::Gammaherpesvirus 68 (gammaHV68, or MHV68) is a naturally occurring rodent pathogen that replicates to high titer in cell culture and is amenable to in vivo experimental evaluation of viral and host determinants of gammaherpesvirus disease. However, the inability of MHV68 to transform primary murine B cells in culture,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02689-07
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abstract::Recent studies using radiolabeled rotavirus lysates have demonstrated a 35-kilodalton viral protein that binds specifically to the surface of MA104 cells (N. Fukuhara, O. Yoshie, S. Kitakoa, and T. Konno, J. Virol. 62:2209-2218, 1988; M. Sabara, J. Gilchrist, G.R. Hudson, and L.A. Babiuk, J. Virol. 53:58-66, 1985). Th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.1.322-330.1990
更新日期:1990-01-01 00:00:00
abstract::Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons wi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.8.4836-4847.2003
更新日期:2003-04-01 00:00:00
abstract::Mammalian cells infected with herpes simplex virus (HSV) express a novel ribonucleotide reductase which is biochemically and immunologically distinct from the uninfected-cell enzyme. Using polyvalent rabbit antiserum raised against partially purified HSV type 2 reductase as well as monoclonal antibodies to HSV type 1 ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.2.591-593.1984
更新日期:1984-02-01 00:00:00
abstract::Bovine leukemia virus (BLV) and human T-cell lymphotropic virus type 1 (HTLV-1) belong to the genus of deltaretroviruses. Their entry into the host cell is supposed to be mediated by interactions of the extracellular (SU) envelope glycoproteins with cellular receptors. To gain insight into the mechanisms governing thi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.16.7956-7967.2002
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abstract::Adenovirus E1B 55K protein cooperates with E1A gene products to induce cell transformation. E1B 55K mediates its effects by binding to and inhibiting the transcriptional activation and growth-suppression functions of the tumor suppressor p53. Previous studies in vivo have suggested that E1B 55K has an active role in r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.4.3146-3154.1998
更新日期:1998-04-01 00:00:00
abstract::Open reading frame (ORF) E4 is a 353-base-pair ORF of bovine papillomavirus type 1. To determine the biological activities of this ORF in mouse C127 cells, we analyzed the effects of two constructed mutations which are predicted to prevent synthesis of ORF E4 proteins while leaving the amino acid sequence encoded by t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.4.1248-1252.1987
更新日期:1987-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.2.397-400.1973
更新日期:1973-08-01 00:00:00
abstract:UNLABELLED:Marburg virus (MARV), which belongs to the virus family Filoviridae, causes hemorrhagic fever in humans and nonhuman primates that is often fatal. MARV is a lipid-enveloped virus that during the replication process extracts its lipid coat from the plasma membrane of the host cell it infects. MARV carries sev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02607-15
更新日期:2015-12-30 00:00:00
abstract::We have studied initiation and regulation of early transcription of simian virus (SV40) DNA in vitro by eucaryotic RNA polymerase II, using both a crude HeLa cell extract and a partially purified calf thymus polymerase supplemented with a HeLa cell S100 fraction. Analysis of initiation sites by primer-directed cDNA sy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.41.2.449-461.1982
更新日期:1982-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.2.684-692.2000
更新日期:2000-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.4.1381-1387.1988
更新日期:1988-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.5.2916-2927.1992
更新日期:1992-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.3154-3162.1994
更新日期:1994-05-01 00:00:00
abstract::The enhancer of human papillomavirus type 16 (HPV-16) is considered to be specific for epithelial cells, in particular for cervical carcinoma-derived cell lines. We reexamined this hypothesis with the complete enhancer as well as nonoverlapping subclones and found all clones to be active in epithelial cell lines deriv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.11.5933-5943.1991
更新日期:1991-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.1143-1146.1976
更新日期:1976-06-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03268-12
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journal_title:Journal of virology
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journal_title:Journal of virology
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更新日期:2003-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02639-07
更新日期:2008-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00348-07
更新日期:2007-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.8.5007-5012.1994
更新日期:1994-08-01 00:00:00
abstract::There is a high degree of intraisolate sequence heterogeneity in the tax gene of human T-cell leukemia virus type I (HTLV-I), although the sequence variation between patients is small compared with that of human immunodeficiency virus type 1. In the present study, we investigated whether naturally occurring amino acid...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2649-2653.1995
更新日期:1995-04-01 00:00:00
abstract::Retrovirus particles each contain two copies of the viral genome in the form of a noncovalently linked RNA dimer. Earlier studies have mapped a cis-acting region near the 5' end of the human immunodeficiency virus type 1 (HIV-1) genome, termed the psi locus, which appears essential for initiation of genomic dimerizati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.5.3407-3414.1997
更新日期:1997-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.1.61-68.1977
更新日期:1977-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.1.75-84.1975
更新日期:1975-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.2.785-793.2006
更新日期:2006-01-01 00:00:00
abstract::Rubella virus contains three structural proteins, capsid, E2, and E1. E2 and E1 are type I membrane glycoproteins that form a heterodimer in the endoplasmic reticulum (ER) before they are transported to and retained in the Golgi complex, where virus assembly occurs. The bulk of unassembled E2 and E1 subunits are not t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.10.7670-7680.1997
更新日期:1997-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.3.1156-1163.1990
更新日期:1990-03-01 00:00:00