Gene Profiling Analysis of ALVAC Infected Human Monocyte Derived Dendritic Cells

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2008 Aug 12

PMID 18691624

Citations 22

Authors

Anke Harenberg

Florine Guillaume

Elizabeth J Ryan

Nicolas Burdin

Franca Spada

Affiliations

Soon will be listed here.

Abstract

The recombinant canarypox virus ALVAC is being extensively studied as vaccine vector for the development of new vaccine strategies against chronic infectious diseases and cancer. However, the mechanisms by which ALVAC initiates the immune response have not been completely elucidated. In order to determine the type of innate immunity triggered by ALVAC, we characterized the gene expression profile of human monocyte derived dendritic cells (MDDCs) upon ALVAC infection. These cells are permissive to poxvirus infection and play a key role in the initiation of immune responses. The majority of the genes that were up-regulated by ALVAC belong to the type I interferon signaling pathway including IRF7, STAT1, RIG-1, and MDA-5. Genes involved in the NF-kappaB pathway were not up-regulated. The gene encoding for the chemokine CXCL10, a direct target of the transcription factor IRF3 was among those up-regulated and DC secretion of CXCL10 following exposure to ALVAC was confirmed by ELISA. Many downstream type I interferon activated genes with anti-viral activity (PKR, Mx, ISG15 and OAS among others) were also up-regulated in response to ALVAC. Among these, ISG15 expression in its unconjugated form by Western blot analysis was demonstrated. In view of these results we propose that ALVAC induces type I interferon anti-viral innate immunity via a cytosolic pattern-recognition-receptor (PRR) sensing double-stranded DNA, through activation of IRF3 and IRF7. These findings may aid in the design of more effective ALVAC-vectored vaccines.

Citing Articles

Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.

Williams L, Shen X, Sawant S, Akapirat S, Dahora L, Tay M PLoS Pathog. 2023; 19(5):e1011359.

PMID: 37256916 PMC: 10284421. DOI: 10.1371/journal.ppat.1011359.

Poxviruses and the immune system: Implications for monkeypox virus.

Saghazadeh A, Rezaei N Int Immunopharmacol. 2022; 113(Pt A):109364.

PMID: 36283221 PMC: 9598838. DOI: 10.1016/j.intimp.2022.109364.

Reappraising the Value of HIV-1 Vaccine Correlates of Protection Analyses.

Klasse P, Moore J J Virol. 2022; 96(8):e0003422.

PMID: 35384694 PMC: 9044961. DOI: 10.1128/jvi.00034-22.

Ex Vivo Evaluation of Mucosal Responses to Vaccination with ALVAC and AIDSVAX of Non-Human Primates.

Herrera C, Veazey R, Lemke M, Arnold K, Kim J, Shattock R Vaccines (Basel). 2022; 10(2).

PMID: 35214645 PMC: 8879115. DOI: 10.3390/vaccines10020187.

The transcription factor CREB1 is a mechanistic driver of immunogenicity and reduced HIV-1 acquisition following ALVAC vaccination.

Tomalka J, Pelletier A, Fourati S, Latif M, Sharma A, Furr K Nat Immunol. 2021; 22(10):1294-1305.

PMID: 34556879 PMC: 8525330. DOI: 10.1038/s41590-021-01026-9.

References

DCunha J, KNIGHT Jr E, Haas A, Truitt R, Borden E . Immunoregulatory properties of ISG15, an interferon-induced cytokine. Proc Natl Acad Sci U S A. 1996; 93(1):211-5. PMC: 40208. DOI: 10.1073/pnas.93.1.211. View

Fischer L, Le Gros F, Mason P, Paoletti E . A recombinant canarypox virus protects rabbits against a lethal rabbit hemorrhagic disease virus (RHDV) challenge. Vaccine. 1997; 15(1):90-6. DOI: 10.1016/s0264-410x(96)00102-8. View

Hutchings C, Gilbert S, Hill A, Moore A . Novel protein and poxvirus-based vaccine combinations for simultaneous induction of humoral and cell-mediated immunity. J Immunol. 2005; 175(1):599-606. DOI: 10.4049/jimmunol.175.1.599. View

Goepfert P, Horton H, McElrath M, Gurunathan S, Ferrari G, Tomaras G . High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects. J Infect Dis. 2005; 192(7):1249-59. DOI: 10.1086/432915. View

Konishi E, Kurane I, Mason P, Shope R, Kanesa-thasan N, Smucny J . Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates. Vaccine. 1998; 16(8):842-9. DOI: 10.1016/s0264-410x(97)00265-x. View

Lenschow D, Lai C, Frias-Staheli N, Giannakopoulos N, Lutz A, Wolff T . IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci U S A. 2007; 104(4):1371-6. PMC: 1783119. DOI: 10.1073/pnas.0607038104. View

Fries L, Tartaglia J, Taylor J, Kauffman E, Meignier B, Paoletti E . Human safety and immunogenicity of a canarypox-rabies glycoprotein recombinant vaccine: an alternative poxvirus vector system. Vaccine. 1996; 14(5):428-34. DOI: 10.1016/0264-410x(95)00171-v. View

Yuan W, KRUG R . Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. EMBO J. 2001; 20(3):362-71. PMC: 133459. DOI: 10.1093/emboj/20.3.362. View

Trifilo M, Montalto-Morrison C, Stiles L, Hurst K, Hardison J, Manning J . CXC chemokine ligand 10 controls viral infection in the central nervous system: evidence for a role in innate immune response through recruitment and activation of natural killer cells. J Virol. 2003; 78(2):585-94. PMC: 368822. DOI: 10.1128/jvi.78.2.585-594.2004. View

10.

van der Burg S, Menon A, Redeker A, Bonnet M, Drijfhout J, Tollenaar R . Induction of p53-specific immune responses in colorectal cancer patients receiving a recombinant ALVAC-p53 candidate vaccine. Clin Cancer Res. 2002; 8(5):1019-27. View

11.

Poulet H, Minke J, Pardo M, Juillard V, Nordgren B, Audonnet J . Development and registration of recombinant veterinary vaccines. The example of the canarypox vector platform. Vaccine. 2007; 25(30):5606-12. DOI: 10.1016/j.vaccine.2006.11.066. View

12.

Salmon-Ceron D, Excler J, Sicard D, Blanche P, Finkielstzjen L, Gluckman J . Safety and immunogenicity of a recombinant HIV type 1 glycoprotein 160 boosted by a V3 synthetic peptide in HIV-negative volunteers. AIDS Res Hum Retroviruses. 1995; 11(12):1479-86. DOI: 10.1089/aid.1995.11.1479. View

13.

Honda K, Taniguchi T . IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006; 6(9):644-58. DOI: 10.1038/nri1900. View

14.

Taylor J, Meignier B, Tartaglia J, Languet B, Vanderhoeven J, Franchini G . Biological and immunogenic properties of a canarypox-rabies recombinant, ALVAC-RG (vCP65) in non-avian species. Vaccine. 1995; 13(6):539-49. DOI: 10.1016/0264-410x(94)00028-l. View

15.

Ryan E, Harenberg A, Burdin N . The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-gamma by Natural Killer (NK) cells enhancing Th1 polarization. Vaccine. 2007; 25(17):3380-90. PMC: 7115637. DOI: 10.1016/j.vaccine.2006.12.048. View

16.

DCunha J, Ramanujam S, WAGNER R, Witt P, KNIGHT Jr E, Borden E . In vitro and in vivo secretion of human ISG15, an IFN-induced immunomodulatory cytokine. J Immunol. 1996; 157(9):4100-8. View

17.

Weinhold K, Matthews T, Graham B, Gorse G, Keefer M, McElrath M . Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group. J Infect Dis. 1998; 177(5):1230-46. DOI: 10.1086/515288. View

18.

Lenschow D, Giannakopoulos N, Gunn L, Johnston C, OGuin A, Schmidt R . Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol. 2005; 79(22):13974-83. PMC: 1280211. DOI: 10.1128/JVI.79.22.13974-13983.2005. View

19.

Wong J, Pung Y, Sze N, Chin K . HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc Natl Acad Sci U S A. 2006; 103(28):10735-40. PMC: 1484417. DOI: 10.1073/pnas.0600397103. View

20.

Banchereau J, Steinman R . Dendritic cells and the control of immunity. Nature. 1998; 392(6673):245-52. DOI: 10.1038/32588. View