Use of recombinant viruses to deliver cytokines influencing the course of experimental bacterial infection

Abstract

SummaryThe feasibility of using viral constructs expressing cytokine genes to influence the course of bacterial infection was tested in mice. The mice were first infected with vaccinia or fowlpox viruses expressing the cytokine of interest, then challenged with the facultative intracellular bacterial pathogen Listeria monocytogenes. The course of infection was assessed by subsequent bacterial counts. Expression of IFN-γ or TNF was protective. Vaccinia virus was more efficient at delivering IFN-γ-mediated protection than was fowlpox virus, which is unable to proliferate in mammalian cells. The effect of vaccinia-IFN-γ was more apparent in the liver, where vaccinia proliferates to high titres (> 10 9 ), than in the spleen, where only 10 3 vaccinia were isolated. Vaccinia virus expressing IL-4 exacerbated infection. Interleukin-4 exacerbation was T cell independent and was reflected in the failure of macrophage activation, possibly due to suppression of NK cells, which are a source of IFN-γ early in infection. The clear indication of protection by some cytokines in this prophylactic model appears to justify further study of the therapeutic effects of cytokine-expressing viruses in chronic bacterial infections, especially where a cytokine defect is suspected.

Identification and immunogenic potential of B cell epitopes of outer membrane protein OmpF of Aeromonas hydrophila in translational fusion with a carrier protein

“…Thus, it can be said that the rEpiF1 fusion antigen generated a mixed immune response. This has an advantage for a vaccine candidate as it has been reported that the antigens that generated mixed immune response conferred better protection in comparison to those which induced only a Th2 response (Cheers et al 1999).…”

Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox

“…This is likely to be the result of the observed combined reduction in antiviral effectors such as CD8 ϩ CTL precursor (CTLp) development, IFN-␥ expression, macrophage activation, and inducible nitric oxide production (4,41). While no reduction in splenic NK cell activity was observed in infected CBA mice (41), a significant reduction was found when SCID mice were infected with VACV expressing IL-4 (4).…”

Recombinant Herpes Simplex Virus Type 1 Expressing Murine Interleukin-4 Is Less Virulent than Wild-Type Virus in Mice

“…TH2 cells are involved in humoral (antibody-mediated) immunity and produce IL-4, IL-5, and IL-10 (31, 34). IL-4 is also an important regulator of isotype switching and the stimulation of immunoglobulin E production in B lymphocytes (8-10).Different reports have provided contradictory evidence suggesting that IL-4 may have either protective or detrimental effects during viral infection (4,11,12,24,29,42). Recently, a recombinant mousepox virus expressing IL-4 was reported to have greatly increased pathogenicity in infected mice (22).…”

“…Different reports have provided contradictory evidence suggesting that IL-4 may have either protective or detrimental effects during viral infection (4,11,12,24,29,42). Recently, a recombinant mousepox virus expressing IL-4 was reported to have greatly increased pathogenicity in infected mice (22).…”