Immunogenicity comparison of interferon beta-1a preparations using the BALB/c mouse model: assessment of a new formulation for use in multiple sclerosis

The in vivo immunogenicity of a new interferon (IFN) beta-1a product (Rebif (R) New Formulation; RNF) was compared with that of two approved recombinant human IFN beta-1a products (Rebif (R) and Avonex (R)). Immunogenic potential was assessed based on time to development of neutralizing antibodies (NAbs) and NAb titer. Female BALB/c mice (six in each group) received RNF, Rebif (R) or (R) (1.0 mu g/mL subcutaneously three times weekly), and serum samples collected on Days 7, 2 1, and 35 (Study 1), or 28, 42, 49, and 60 (Study 2) were assayed for NAbs. In Study 1, no mice had NAbs at Day 7, but by Day 21 one mouse in the RNF group had NAbs, compared with three and four mice in the Rebif (R) and Avonex (R) groups, respectively. Results were similar in Study 2. All control mice were NAb negative; all actively treated mice had NAbs by day 35 or 42. Throughout Study 1, NAb titers were lowest in the RNF group and highest in the Avonex (R) group, and at day 35, NAb titers were significantly lower in the RNF group than the Rebif (R) group (p = 0.037). Results indicate that, on a gram-for-gram basis, RNT appears less immunogenic than Rebif (R) or Avonex (R).