AUTHOR=Cobb Jacob , Rawson Jeffrey , Gonzalez Nelson , Hensel Michael , Kandeel Fouad , Husseiny Mohamed I. 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.667897

DOI=10.3389/fimmu.2021.667897

ISSN=1664-3224

ABSTRACT=<p>A therapy that includes an oral vaccine for type 1 diabetes (T1D) using live attenuated <italic>Salmonella</italic> MvP728 (Δ<italic>htrA/</italic>Δ<italic>purD</italic>), 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 <italic>Salmonella</italic> mutant (Δ<italic>msbB</italic>) 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) <italic>via</italic> detoxification of lipid A. This mutant strain proved to have highly reduced pathogenic side effects. <italic>Salmonella</italic> strain Δ<italic>msbB</italic> 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<italic>htrA/</italic>Δ<italic>purD</italic>. Additionally, the <italic>Salmonella msbB</italic> mutant resulted in higher rates of host cell infection. These results further demonstrate the potential of an oral <italic>Salmonella</italic>-based combined therapy in the treatment of early T1D.</p>