Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC

• Main Authors: Shushan Harutyunyan, Irene Neuhauser, Alexandra Mayer, Michael Aichinger, Valéria Szijártó, Gábor Nagy, Eszter Nagy, Petra Girardi, Frank J. Malinoski, Tamás Henics
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Vaccines
• Subjects: vaccine; <i>Shigella</i>; cross-protection; rough; non-invasive; ETEC
• Online Access: https://www.mdpi.com/2076-393X/8/4/689

<i>Shigella</i> spp. and enterotoxigenic <i>Escherichia coli</i> (ETEC) remain the two leading bacterial causes of diarrheal diseases worldwide. Attempts to develop preventive vaccines against Shigella and ETEC have not yet been successful. The major challenge for a broad Shigella vaccine is the serotype-specific immune response to the otherwise protective LPS O-antigen. ETEC vaccines mainly rely on the heat-labile enterotoxin (LT), while heat-stable toxin (ST) has also been shown to be an important virulence factor. <b>Methods</b>: We constructed a combined Shigella and ETEC vaccine (ShigETEC) based on a live attenuated Shigella strain rendered rough and non-invasive with heterologous expression of two ETEC antigens, LTB and a detoxified version of ST (ST_N12S). This new vaccine strain was characterized and tested for immunogenicity in relevant animal models. <b>Results</b>: Immunization with ShigETEC resulted in serotype independent protection in the mouse lung shigellosis model and induced high titer IgG and IgA antibodies against bacterial lysates, and anti-ETEC toxin antibodies with neutralizing capacity. <b>Conclusions</b>: ShigETEC is a promising oral vaccine candidate against Shigella and ETEC infections and currently in Phase 1 testing.