title: Comparative analysis of tropism between canarypox (ALVAC) and vaccinia viruses reveals a more restricted and preferential tropism of ALVAC for human cells of the monocytic lineage.
abstract: The poxviruses including canarypox (ALVAC) and vaccinia viruses are promising vaccine vectors in humans, but little is known about their biology in human cells. 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 towards 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 that could be enhanced upon their activation. The observed preferential infection of ALVAC or vaccinia virus to monocytes was the result of preferential binding to this population, rather than lineage-specific differences in the expression of viral genes. Moreover, the level of CD14 expression on monocytes correlated with their preference to be infected with ALVAC or vaccinia virus. Both ALVAC and vaccinia viruses could infect immature monocyte derived dendritic cells (MDDCs), but only ALVAC infection induced their subsequent maturation. Vaccinia virus, however, showed greater tropism for mature MDDCs compared to ALVAC. Infection in human bone marrow cultures 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. These findings have implications in terms of choosing optimal pox virus derived vectors as vaccines in terms of reducing clinical reactogenicity and inducing dendritic cell (DC) maturation.
authors.affiliation: Hawaii AIDS Clinical Research Program, Department of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA.
authors.forename: Qigui
authors.initials: Q
authors.lastname: Yu
authors.forename: Brad
authors.initials: B
authors.lastname: Jones
authors.forename: Ningjie
authors.initials: N
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Sidrah
authors.initials: S
authors.lastname: Ahmad
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Mark
authors.initials: M
authors.lastname: Parrington
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
mesh_terms: D023201:CD40 Ligand / Q000378:metabolism; D028121:Canarypox virus / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000821:virology*; D013997:Time Factors; D014616:Vaccinia virus / Q000235:genetics / Q000502:physiology*
chemical_list: D018950:Lipopolysaccharide Receptors; D023201:CD40 Ligand