Purchase this article with an account.
H. Ghiasi, C. Shahbazian, Y. Osorio; Comparison Of Adjuvant Efficacy Of Hsv–1 Recombinant Viruses Expressing Different Cytokine Genes Following Ocular Hsv–1 Challenge . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2257.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the adjuvant effect of cytokines in improving vaccine efficacy against ocular virus replication, eye disease, and latency following ocular challenge of mice immunized with recombinant viruses expressing different cytokine genes. Methods: We constructed HSV–1 recombinant viruses expressing various cytokine genes in a LAT–γ34.5–deletion background. BALB/c mice were immunized ip with IL–12p35, IL–12p40, IL–12p35 + IL–12p40, or IL–4 expressing recombinant viruses. The efficacy of each vaccine against virus replication in the eye, survival, eye disease, and latency were examined by assaying neutralizing antibody, T cell and macrophage responses, and the expression of 32 cytokines/chemokines in immunized mice. Controls included mice immunized with parental LAT–γ34.5–deletion virus and mice immunized with the avirulent strain KOS. Results: Corneal scarring and survival were similar for all vaccine groups. Mice immunized with recombinant HSV–1 expressing IL–12p35 had higher neutralizing antibody titers, lower virus replication in the eye, and lower level of latency than the other vaccine groups. Splenocytes isolated from mice vaccinated with HSV–IL12p35 had higher levels of IL–12p70, IFN–γ, and IL–3 than any other group. All vaccine groups, however, had similar levels of IL–2, IL–12p40, TNF–α, and IL–4. Conclusions: In addition to altering the immune response, recombinant virus vaccines expressing cytokines can increase the efficacy of protection against infection from disease. Of the five recombinant virus vaccines that we have constructed and tested in vivo, the order of improved vaccine efficacy is IL–12p35 > KOS > IL–12p40 = IL–12p35 + IL–12p40 = IL–4 > IL–2 > IFN–γ = Parental virus.
This PDF is available to Subscribers Only