Research of immunogenicity of mycobacteriophage D29 toward tuberculosis therapy / 中华传染病杂志

ABSTRACT

Objective To investigate the immunogenicity of mycobacteriophage D29 (phage D 29) in guinea pig models with different delivery routes,and provide information for the application of phages in tuberculosis (TB) therapy.Methods Hartley guinea pigs were administrated with phage D29 through inhalation,intranasal drop or subcutaneous injection for 6 times within 35 days.7H9 broth aerosol inhalation and 0.85 ％ NaCl solution aerosol inhalation were set as solvent and negative controls,respectively.Anti-phage D29 neutralizing antibodies in sera collected weekly were measured by phage reduction neutralizing test (PRNT) and cytokine levels (interleukin-2,interleukin-4 and interferon-γ) were detected at day 35 by enzyme linked immunosorbent assay (ELISA).The data were analyzed by ANOVA and nonparametric test.ResultsNeutralizing antibodies were both negative in two control groups,while low-titer neutralizing antibodies (below 1 ∶ 100) appeared in inhalation and intranasal drop groups only at day 7 and day 14. Nevertheless, neutralizing antibodies were continuously detected in subcutaneous injection group,which increased rapidly and reached 1∶ 16 365.6 at day 35. After 35 days of experiments,serum concentrations of interleukin-2 (x2 =2.7605,P＞0.05),interleukin-4 (F=2.17,P＞0.05) and interferon-γ(F=0.75,P＞0.05) among three treatment groups and two control groups were all not significantly different.ConclusionsThe titer of anti-phage 29 neutralizing antibodies induced by inhalation or intranasal drop administration of phage D29 are both significantly lower than subcutaneous injection.Phage D29 administration doesn’t change the levels of cytokines,which indicates that it may not break the helper T cell (Th)1/Th2 balance.