AUTHOR=Lu Ti , Das Sayan , Howlader Debaki R. , Zheng Qi , Ratnakaram Siva Sai Kumar , Whittier Sean K. , Picking William D. , Picking Wendy L. 

TITLE=L-DBF Elicits Cross Protection Against Different Serotypes of Shigella spp

JOURNAL=Frontiers in Tropical Diseases

VOLUME=2

YEAR=2021

URL=https://www.frontiersin.org/journals/tropical-diseases/articles/10.3389/fitd.2021.729731

DOI=10.3389/fitd.2021.729731

ISSN=2673-7515

ABSTRACT=<p>Shigellosis is a severe diarrheal disease caused by members of the genus <italic>Shigella</italic>, with at least 80 million cases and 700,000 deaths annually around the world. The type III secretion system (T3SS) is the primary virulence factor used by the shigellae, and we have previously demonstrated that vaccination with the type T3SS proteins IpaB and IpaD, along with an IpaD/IpaB fusion protein (DBF), protects mice from <italic>Shigella</italic> infection in a lethal pulmonary model. To simplify the formulation and development of the DBF <italic>Shigella</italic> vaccine, we have genetically fused LTA1, the active subunit of heat-labile toxin from enterotoxigenic <italic>E. coli</italic>, with DBF to produce the self-adjuvanting antigen L-DBF. Here we immunized mice with L-DBF <italic>via</italic> the intranasal, intramuscular, and intradermal routes and challenged them with a lethal dose of <italic>S. flexneri</italic> 2a. While none of the mice vaccinated intramuscularly or intradermally were protected, mice vaccinated with L-DBF intranasally were protected from lethal challenges with <italic>S. flexneri</italic> 2a, <italic>S. flexneri</italic> 1b, <italic>S. flexneri</italic> 3a, <italic>S. flexneri</italic> 6, and <italic>S. sonnei</italic>. Intranasal L-DBF induced both B cell and T cell responses that correlated with protection against <italic>Shigella</italic> infection. Our results suggest that L-DBF is a candidate for developing an effective serotype-independent vaccine against <italic>Shigella</italic> spp.</p>