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Colonization factors or Coli surface antigens (CFs or CS) are important virulence factors of Enterotoxigenic E. coli (ETEC) that mediate intestinal colonization and accordingly are targets of vaccine development efforts. CS6 is a highly prevalent CF associated with symptomatic ETEC infection both in endemic populations and amongst travelers. In this study, we used an Aotus nancymaae non-human primate ETEC challenge model with a CS6 + ETEC strain, B7A, to test the immunogenicity and protective efficacy (PE) of a recombinant CS6-based subunit vaccine. Specifically, we determined the ability of dscCssBA, the donor strand complemented recombinant stabilized fusion of the two subunits of the CS6 fimbriae, CssA and CssB, to elicit protection against CS6 + ETEC mediated diarrhea when given intradermally (ID) with the genetically attenuated double mutant heat-labile enterotoxin LT(R192G/L211A) (dmLT). ID vaccination with dscCssBA + dmLT induced strong serum antibody responses against CS6 and LT. Importantly, vaccination with dscCssBA + dmLT resulted in no observed diarrheal disease (PE = 100%, p = 0.03) following B7A challenge as compared to PBS immunized animals, with an attack rate of 62.5%. These data demonstrate the potential role that CS6 may play in ETEC infection and that recombinant dscCssBA antigen can provide protection against challenge with the homologous CS6 + ETEC strain, B7A, in the Aotus nancymaae diarrheal challenge model. Combined, these data indicate that CS6, and more specifically, a recombinant engineered derivative should be considered for further clinical development.

This research work took place up to and during 1997 and the results hereafter are from that research. However, since then there has been additional research work. For the purposes of this paper the principles remain fundamentally consistent; however, the reader should recognise the concept has been refined since the paper was initially published. The butt fusion procedures used in the UK water and gas industries, which determine the total time taken to complete a successful joint, have remained largely unchanged since their harmonisation in 1990. The parameters evolved to suit manually operated butt fusion machines and reflected the fact that the minimum achievable heater plate removal time, for up to 250 mm diameter, was between 6 and 8 s, during which the operator had to manually operate a hand pump to remove the heater. With standardisation of automatic butt fusion, and typical heater plate removal times of 2 s, the potential exists to reduce considerably the on site jointing time and thus enable substantial financial savings. Trials to date have been exclusive to second generation medium density polyethylene PE80, due to its known tolerance to variances in jointing parameters, which can occur with manual machines working in site conditions. Further work to determine the fast weld parameters of third generation high density polyethylene PE100 is planned for the future.