Efficacy Of Inactivated Whole-virion Influenza Vaccine And Adjucant In Type 1 Diabetic Mice

This article consists of four parts.1) brief introduction of influenza virus, influenza vaccine,vaccine adjuvants and diabetes mellitus; 2) susceptibility of type 1 diabetic mice to an H5N1 virus; 3) evaluation of antibody reponses and protection induced by inactivated whole-virion H5N1 influenza vaccine in type 1 diabetic mice; 4)efficacy of MF-59 and AL(OH)3 as adjuvants to inactivated whole-virion H5N1 influenza vaccine in type 1 diabetic mice.(1), brief introduction of influenza virus, influenza vaccine,vaccine adjuvants and diabetes mellitus. It serves as an overview which outlines the basic characteristics of influenza virus, the influenza vaccine,hazard of H5N1 influenza virus,the prevalence of diabetes mellitus as well as the progress in research of experimental diabetic animal models.(2), susceptibility of type 1 diabetic mice to an H5N1 virus. Male BALB/c mice were treated with streptozotocin (STZ) to induce type 1 diabetes. Healthy and diabetic mice were killed and single spleenic cell suspensions were prepared. After staining, proportions of CD4+and CD8+T cell subsets were measured by flow cytometry analyses. Susceptibility of diabetic mice to H5N1 virus was evaluated by comparing the median lethal dose (LD50) and the lung virus titers with those of the healthy after the viral infection. The results showed that the CD4+proportion in type 1 diabetic mice was lower than healthy mice, while the CD8+proportion in diabetic mice was higher. The CD4+/CD8+ ratio was significantly lower in diabetic mice than in healthy mice. After infection, lung virus titers in diabetic mice were higher than healthy mice and the virus remained in diabetic mice for a longer time, the survival rates of diabetic mice were also lower than those of healthy mice.(3), evaluation of antibody reponses and protection induced by inactivated whole-virion H5N1 influenza vaccine in type 1 diabetic mice. Inactivated influenza A/Vietnam/1194/2004 (H5N1) virus vaccine was diluted into various dosages in a volume of 200μl with PBS. The diabetic and healthy mice were immunized i.p. once with the diluted vaccine of 0.1,0.33,1.0,3.3 and 10μg separately. The mice as control were injected i.p. with 200μl of PBS. Serum specific IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and the serum neutralization activity was measured by hemagglutination inhibition assay(HI). The mice were challenged with H5N1 influenza virus at a lethal dose, and the protective effect of vaccine was observed to provide reference for clinical studies. The results showed that inactivated H5N1 vaccine induced protective antibody in diabetic mice, but the antibody responses were postponed and weakened. Compared with healthy mice, diabetic mice could be well protected with a single dose of immunization when the amount of the antigen increased.(4), efficacy of MF-59 and Al(OH)3 as adjuvants to inactivated whole-virion H5N1 influenza vaccine in type 1 diabetic mice. Mice were immunized with a single dose of the inactivated vaccine, alone or adjuvanted with MF59 or Al(OH)3. After four weeks, they were challenged with a lethal dose of H5N1 virus. The antibody responses, survival rates, lung virus titers and body weight changes were tested to compare the protective effects of immunization in both diabetic and healthy mice. The results showed that both MF59 and Al(OH)3 significantly enhanced the antibody responses to inactivated whole-virion H5N1 vaccine in diabetic mice, but the MF59-adjuvanted groups showed significantly higher antibody titers than the Al(OH)3-adjuvanted groups. The addition of MF59 or Al(OH)3 to the vaccine led to a conversion of immune responses from a Th1-biased response to an enhanced mixed Th1/Th2 profile. The MF59 showed better adjuvant effect than the Al(OH)3.