F41 pili as protective antigens of enterotoxigenic Escherichia coli that produce F41, K99, or both pilus antigens

Abstract

Pigs suckling dams that have been vaccinated with pilus antigen are protected against challenge with enterotoxigenic Escherichia coli (ETEC) strains that express the same pilus antigen. However, some ETEC strains express more than one pilus antigen. Pregnant swine were vaccinated either with E. coli HB101 that harbored a recombinant plasmid coding for F41 expression (F41+) or with the HB101 parent strain that carries the pHC79 vector (F41-). Suckling pigs born to vaccinated dams were challenged with ETEC that expressed either K99, F41, or both pilus antigens. Production of F41 in vivo was demonstrated by immunofluorescence assay of sections of ileum and by seroconversion against F41 antigen by pigs challenged with F41+ and K99+ F41+ ETEC strains. The F41+ vaccine protected against challenge with an F41+ ETEC strain. In contrast, F41+ vaccination did not protect against challenge with K99+ or K99+ F41+ ETEC strains. The F41vaccine did not protect against challenge with any strain used. The results indicate that K99Q F41+ ETEC strains produce F41 antigen in the small intestine during disease and that F41+ vaccination can be a protective antigen if the challenge strain expresses only F41 antigen, but that F41+ vaccination may not protect against strains that produce both K99 and F41 antigens. Enterotoxigenic Escherichia coli (ETEC) strains colonize the small intestine, secrete enterotoxins, and cause diarrhea. Colonization is facilitated by pili (fimbriae). Pili facilitate adherence of ETEC to intestinal mucosa (13). Pilus adhesins that are known to be important in ETEC infections of neonatal animals are K88, K99, 987P, FY, and F41 (3, 15, 19, 21, 23, 25, 30). The K88, K99, and 987P pili are also designated F4, F5, and F6, respectively (24). The F41 pilus was originally referred to as anionic K99 (18). Pilus adhesins known to be important in humans are colonization factor antigens (CFA) I and 11 (10). Some ETEC strains produce more than one of these adhesins. For example, many strains that produce K99 also produce F41 (19, 20); some strains that produce K88 also produce 987P (28); and the CFA II of human ETEC is a complex of three different pili designated CS1, CS2, and CS3 (10). Purified pilus vaccines protect against challenge with ETEC strains that produce the same pilus antigen (1, 9, 17). There are two lines of evidence that K99+ vaccines protect against challenge with ETEC strains that produce both K99 and F41 (K99+ F41+). First, a purified K99 pilus vaccine protects pigs and calves from challenge with K99+ ETEC strains 431 and B44, respectively (1, 17). Both of these strains were subsequently shown to be K99+ F41+ (19, 20). The purified K99 pilus (7) vaccine that was used (1, 17) did not contain F41, since it was prepared from a K-12 transconjugant that produces K99 but not F41 (8, 19). It was the absence of F41 (anionic K99) from these purified K99 pilus preparations that resulted in the controversy (7, 8, 18-20), leading to recognition that F41 is distinct from K99 (4, 8, 19, 31). Second, monoclonal antibod...

Protection Against Neonatal Escherichia coli Diarrhoea in Pigs by Vaccination of Sows with a New Vaccine that Contains Purified Enterotoxic E. coli Virulence Factors F4ac, F4ab, F5 and F6 Fimbrial Antigens and Heat‐Labile E. coli Enterotoxin (LT) Toxoid

“…Our finding that vaccination of dams with the F5 antigen can protect their offspring against challenge with an E. coli strain that expresses both F5 and F41 confirms earlier work in both pigs (Morgan et al., 1978) and cattle (Acres et al., 1979). Conversely, it has been shown that vaccination with a vaccine containing F41 only will not protect against an E. coli strain expressing both F5 and F41 (Runnel et al., 1987).…”

Inhibitory effects of Lactobacillus casei upon the adhesion of enterotoxigenic Escherichia coli K99 to the intestinal mucosa in gnotobiotic lambs

“…The following methods are in use: 1. Vaccination against bacterial adhesion factors (Levine et al, 1983;Runnels et al, 1987). 2.…”

In vivo emergence of enterotoxigenic Escherichia coli variants lacking genes for K99 fimbriae and heat-stable enterotoxin

“…in sealed tubes, stored at room temperature in the dark, with a nonselective transfer (without cloning or selection) to fresh medium every 3 years. All inocula came from samples of the same culture, which was prepared and stored at -70°C, as reported previously (12,19), for more than 1 year. Samples were thawed and diluted in Trypticase soy broth (BBL) just before inoculation into pigs.…”

“…The experiment in suckling pigs involved the newborn pigs of five gilts (primiparous swine). In a separate study (19), four of these gilts received a vaccine containing F41 fimbriae, and the other received a placebo. None of them was vaccinated against K99.…”

“…Titers of K99 and F41 antibody in colostral whey were determined by enzyme-linked immunosorbent assay of samples collected from the gilts at farrowing (19). When the pigs were 1 to 7 h old, each was inoculated intragastrically with 1010 CFU of strain 431 (19). Rectal swabs were collected from the pigs daily from 1 to 5 days postinoculation (p.i.)…”