Dr Pål Puntervoll, NORCE Norwegian Research Centre AS; Prof. Halvor Sommerfelt, University of Bergen; Dr Arne Taxt, University of Bergen; Prof. James Nataro, University of Virginia School of Medicine; Prof. John Clements, Tulane University Health Sciences Center/Tulane Educational Fund; Dr Weiping Zang, South Dakota State University
15 - 20 million travelers suffer from episodes of diarrhea annually and enterotoxigenic Escherichia coli (ETEC) is considered the most common cause. ETEC producing the heat-stable toxin (ST) was recently shown to be among the top four pathogens causing moderate-to-severe diarrhea. No broadly effective vaccines are available to protect humans against ST-related ETEC diarrhea. ST is highly conserved and a hence very attractive alternative vaccine target with the potential for broad protection. However, ST must be coupled to a carrier to become immunogenic and must be engineered to remove toxicity and the potential to elicit an immune response that cross-react with the human endogenous peptides guanylin and uroguanylin.
A screen of 361, all possible single-amino acid mutants of heat-stable toxin (ST) has identified a panel of immunogenic non-toxic ST variants. Data suggest that cross-reaction with uroguanilyn and guanilyn is partial and of low affinity. Mapping of epitopes for neutralizing antibodies have identified both safe epitopes and cross-reacting epitopes. The technology provides ST mutants that can be used as ETEC vaccine components. These results allowed the rational design of an ST-based vaccine component that is produced by chemical synthesis of non-toxic variants of ST. Chemical conjugation method is used for coupling mutant ST toxin to a protein carrier.
BTO AS is the patent estate holder and has the commercialization rights. We are looking for a licensing partner who would offer market access in all major markets (i.e. Europe, US, Asia) and with experience in vaccine development. In Asia some restrictions exist concerning commercialization.
Results from testing vaccine candidates in animal model will be known in Q2 2019.
Priority date: 20 February 2013 INT
Application Number: PCT/IB2014/000267; INT Publication Number: WO2014128555 A2
Patent granted in the US (US10166279B2)
Pending approval in Europe and China
Taxt A et al. Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun. (2010)
Taxt AM et al. Characterization of immunological cross-reactivity between enterotoxigenic Escherichia coli heat-stable toxin and human guanylin and uroguanylin. Infect Immun. (2014)