Oral Salmonella msbB Mutant as a Carrier for a Salmonella-Based Vaccine for Prevention and Reversal of Type 1 Diabetes

Abstract

A therapy that includes an oral vaccine for type 1 diabetes (T1D) using live attenuated <i>Salmonella</i> MvP728 (Δ<i>htrA/</i>Δ<i>purD</i>), cytokines (IL10 and TGFβ) and preproinsulin (PPI) antigen in combination with a sub-therapeutic dose of anti-CD3 mAb was developed by our team. The vaccine combination therapy reduced insulitis and prevented and reversed diabetes in non-obese diabetic (NOD) mice. Here, we show the effectiveness of an alternative <i>Salmonella</i> mutant (Δ<i>msbB</i>) as a carrier strain, which is anticipated to have lower risks of an inflammatory response and septicemia as a result of modification in the lipopolysaccharide (LPS) <i>via</i> detoxification of lipid A. This mutant strain proved to have highly reduced pathogenic side effects. <i>Salmonella</i> strain Δ<i>msbB</i> expressed autoantigens and in combination with cytokines and anti-CD3 mAb, successfully prevented and reversed T1D to levels comparable to the previously used carrier strain Δ<i>htrA/</i>Δ<i>purD</i>. Additionally, the <i>Salmonella msbB</i> mutant resulted in higher rates of host cell infection. These results further demonstrate the potential of an oral <i>Salmonella</i>-based combined therapy in the treatment of early T1D.