Summary
Poxviruses including canarypox (ALVAC) and vaccinia viruses have, in recent years, received considerable attention as live vectors for the development of vaccines against infectious diseases such as AIDS, malaria, and tuberculosis. However, the cellular targets for viral infection within the human immune system and the consequences of infection for cells involved in the generation of immune responses have not been clearly delineated. Using recombinant enhanced green fluorescence protein (EGFP)-expressing ALVAC and vaccinia viruses, we have focused here on a side-by-side comparison of ALVAC and vaccinia virus tropism for cells from human peripheral blood and bone marrow. Both ALVAC and vaccinia viruses showed a strong bias toward monocyte infection. ALVAC minimally infected CD19+ B cells and was unable to infect ex vivo NK cells and T lymphocytes, whereas vaccinia virus could infect B lymphocytes and NK cell populations. Vaccinia virus was also able to infect T lymphocytes at low but detectable levels which could be enhanced upon their activation. Both ALVAC and vaccinia viruses could infect immature monocyte-derived dendritic cells (MDDCs), but only ALVAC infection induced their subsequent maturation. Infection in human bone marrow cells showed that ALVAC infection was restricted to a myelomonocytoid cell-specific CD33+ cell population, while vaccinia virus showed a strong, but not exclusive, preference for these cells.
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Moss, B. (1992) Vaccinia and other poxvirus expression vectors. Curr Opin Biotechnol 3, 518–22.
Moss, B., Fuerst, T.R., Flexner, C., Hugin, A. (1988) Roles of vaccinia virus in the development of new vaccines. Vaccine 6, 161–3.
Moss, B., Flexner, C. (1987) Vaccinia virus expression vectors. Annu Rev Immunol 5, 305–24.
Bostock, C.J. (1990) Viruses as vectors. Vet Microbiol 23, 55–71.
Fries, L.F., Tartaglia, J., Taylor, J., Kauffman, E.K., Meignier, B., Paoletti, E., Plotkin, S. (1996) Human safety and immunogenicity of a canarypox-rabies glycoprotein recombinant vaccine: an alternative poxvirus vector system. Vaccine 14, 428–34.
McFadden, G. (2005) Poxvirus tropism. Nat Rev Microbiol 3, 201–13.
Krugman, S., Katz, S.L. (1969) Smallpox vaccination. N Engl J Med 281, 1241–2.
Welter, J., Taylor, J., Tartaglia, J., Paoletti, E., Stephensen, C.B. (2000) Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines. J Virol 74, 6358–67.
Tartaglia, J., Jarrett, O., Neil, J.C., Desmettre, P., Paoletti, E. (1993) Protection of cats against feline leukemia virus by vaccination with a canarypox virus recombinant, ALVAC-FL. J Virol 67, 2370–5.
Salmon-Ceron, D., Excler, J.L., Finkielsztejn, L., Autran, B., Gluckman, J.C., Sicard, D., Matthews, T.J., Meignier, B., Valentin, C., El Habib, R., Blondeau, C., Raux, M., Moog, C., Tartaglia, J., Chong, P., Klein, M., Milcamps, B., Heshmati, F., Plotkin, S. (1999) Safety and immunogenicity of a live recombinant canarypox virus expressing HIV type 1 gp120 MN MN tm/gag/protease LAI (ALVAC-HIV, vCP205) followed by a p24E-V3 MN synthetic peptide (CLTB-36) administered in healthy volunteers at low risk for HIV infection. AGIS Group and L’Agence Nationale de Recherches sur Le Sida. AIDS Res Hum Retroviruses 15, 633–45.
Karnasuta, C., Paris, R.M., Cox, J.H., Nitayaphan, S., Pitisuttithum, P., Thongcharoen, P., Brown, A.E., Gurunathan, S., Tartaglia, J., Heyward, W.L., McNeil, J.G., Birx, D.L., de Souza, M.S. (2005) Antibody-dependent cell-mediated cytotoxic responses in participants enrolled in a phase I/II ALVAC-HIV/AIDSVAX B/E prime-boost HIV-1 vaccine trial in Thailand. Vaccine 23, 2522–9.
Tartaglia, J., Perkus, M.E., Taylor, J., Norton, E.K., Audonnet, J.C., Cox, W.I., Davis, S.W., van der Hoeven, J., Meignier, B., Riviere, M., et al (1992) NYVAC: a highly attenuated strain of vaccinia virus. Virology 188, 217–32.
Marovich, M.A., Mascola, J.R., Eller, M.A., Louder, M.K., Caudrelier, P.A., El-Habib, R., Ratto-Kim, S., Cox, J.H., Currier, J.R., Levine, B.L., June, C.H., Bernstein, W.B., Robb, M.L., Schuler-Thurner, B., Steinman, R.M., Birx, D.L., Schlesinger-Frankel, S. (2002) Preparation of clinical-grade recombinant canarypox-human immunodeficiency virus vaccine-loaded human dendritic cells. J Infect Dis 186, 1242–52.
Marovich, M.A. (2004) ALVAC-HIV vaccines: clinical trial experience focusing on progress in vaccine development. Expert Rev Vaccines 3, S99–S104.
Tartaglia, J., Cox, W.I., Taylor, J., Perkus, M., Riviere, M., Meignier, B., Paoletti, E. (1992) Highly attenuated poxvirus vectors. AIDS Res Hum Retroviruses 8, 1445–7.
Cox, W.I., Tartaglia, J., Paoletti, E. (1993) Induction of cytotoxic T lymphocytes by recombinant canarypox (ALVAC) and attenuated vaccinia (NYVAC) viruses expressing the HIV-1 envelope glycoprotein. Virology 195, 845–50.
Santra, S., Schmitz, J.E., Kuroda, M.J., Lifton, M.A., Nickerson, C.E., Lord, C.I., Pal, R., Franchini, G., Letvin, N.L. (2002) Recombinant canarypox vaccine-elicited CTL specific for dominant and subdominant simian immunodeficiency virus epitopes in rhesus monkeys. J Immunol 168, 1847–53.
Pal, R., Venzon, D., Letvin, N.L., Santra, S., Montefiori, D.C., Miller, N.R., Tryniszewska, E., Lewis, M.G., VanCott, T.C., Hirsch, V., Woodward, R., Gibson, A., Grace, M., Dobratz, E., Markham, P.D., Hel, Z., Nacsa, J., Klein, M., Tartaglia, J., Franchini, G. (2002) ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency. J Virol 76, 292–302.
Adler, S.P., Plotkin, S.A., Gonczol, E., Cadoz, M., Meric, C., Wang, J.B., Dellamonica, P., Best, A.M., Zahradnik, J., Pincus, S., Berencsi, K., Cox, W.I., Gyulai, Z. (1999) A canarypox vector expressing cytomegalovirus (CMV) glycoprotein B primes for antibody responses to a live attenuated CMV vaccine (Towne). J Infect Dis 180, 843–6.
Ghose, A., Iakhnina, E., Spaner, D., Tartaglia, J., Berinstein, N.L. (2000) Immunogenicity of whole-cell tumor preparations infected with the ALVAC viral vector. Hum Gene Ther 11, 1289–301.
Konishi, E., Kurane, I., Mason, P.W., Shope, R.E., Kanesa-Thasan, N., Smucny, J.J., Hoke, C.H., Jr., Ennis, F.A. (1998) Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates. Vaccine 16, 842–9.
Ignatius, R., Marovich, M., Mehlhop, E., Villamide, L., Mahnke, K., Cox, W.I., Isdell, F., Frankel, S.S., Mascola, J.R., Steinman, R.M., Pope, M. (2000) Canarypox virus-induced maturation of dendritic cells is mediated by apoptotic cell death and tumor necrosis factor alpha secretion. J Virol 74, 11329–38.
Chahroudi, A., Chavan, R., Kozyr, N., Waller, E.K., Silvestri, G., Feinberg, M.B. (2005) Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor. J Virol 79, 10397–407.
Sanchez-Puig, J.M., Sanchez, L., Roy, G., Blasco, R. (2004) Susceptibility of different leukocyte cell types to Vaccinia virus infection. Virol J 1, 10.
Norbury, C.C., Malide, D., Gibbs, J.S., Bennink, J.R., Yewdell, J.W. (2002) Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat Immunol 3, 265–71.
Ercolani, L., Florence, B., Denaro, M., Alexander, M. (1988) Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. J Biol Chem 263, 15335–41.
Yu, Q., Kovacs, C., Yue, F.Y., Ostrowski, M.A. (2004) The role of the p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and phosphoinositide-3-OH kinase signal transduction pathways in CD40 ligand-induced dendritic cell activation and expansion of virus-specific CD8+ T cell memory responses. J Immunol 172, 6047–56.
Yu, Q., Gu, J.X., Kovacs, C., Freedman, J., Thomas, E.K., Ostrowski, M.A. (2003) Cooperation of TNF family members CD40 ligand, receptor activator of NF-kappa B ligand, and TNF-alpha in the activation of dendritic cells and the expansion of viral specific CD8+ T cell memory responses in HIV-1-infected and HIV-1-uninfected individuals. J Immunol 170, 1797–805.
Ostrowski, M.A., Justement, S.J., Ehler, L., Mizell, S.B., Lui, S., Mican, J., Walker, B.D., Thomas, E.K., Seder, R., Fauci, A.S. (2000) The role of CD4 + T cell help and CD40 ligand in the in vitro expansion of HIV-1-specific memory cytotoxic CD8+ T cell responses. J Immunol 165, 6133–41.
Brinkman-Van der Linden, E.C., Angata, T., Reynolds, S.A., Powell, L.D., Hedrick, S.M., Varki, A. (2003) CD33/Siglec-3 binding specificity, expression pattern, and consequences of gene deletion in mice. Mol Cell Biol 23, 4199–206.
Freeman, S.D., Kelm, S., Barber, E.K., Crocker, P.R. (1995) Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules. Blood 85, 2005–12.
Imamura, R., Miyamoto, T., Yoshimoto, G., Kamezaki, K., Ishikawa, F., Henzan, H., Kato, K., Takase, K., Numata, A., Nagafuji, K., Okamura, T., Sata, M., Harada, M., Inaba, S. (2005) Mobilization of human lymphoid progenitors after treatment with granulocyte colony-stimulating factor. J Immunol 175, 2647–54.
Yu, Q., Jones, B., Hu, N., Chang, H., Ahmad, S., Liu, J., Parrington, M., Yewdell, J., Ostrowski, M.A. (2006) Comparative analysis of tropism between Canarypox (ALVAC) and Vacciniaviruses reveals a more restricted and preferential tropism of ALVAC for human cells of the monocytic lineage. Vaccine 24, 6376–91.
Acknowledgments
This work was carried out with funding from CFAR at University of Washington (AI 27757), R21 from NIAID/NIH (AI073250), Research Facilities Improvement Program Grant Number C06 RR015481-01 from NIH, Hawaii Community Foundation, OHTN, CIHR, Amfar, and Sanofi-UTRP program. Text and figures were modified from Vaccine (2006) 24, 6376–6391 (33)with permission from the Elsevier Corporate.
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Yu, Q., Hu, N., Ostrowski, M. (2009). Poxvirus Tropism for Primary Human Leukocytes and Hematopoietic Cells. In: Hicks, B.W. (eds) Viral Applications of Green Fluorescent Protein. Methods in Molecular Biology™, vol 515. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-559-6_22
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DOI: https://doi.org/10.1007/978-1-59745-559-6_22
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