The adjuvant effect of Gantrez®AN nanoparticles on oral vaccination of pigs and mice with F4 fimbriae is strongly influenced by polymer degradation

We analysed the adjuvant effect of Gantrez nanoparticles NP on oral immunisation of pigs and mice with F4 fimbriae. The animals were vaccinated with F4, F4 encapsulated in Gantrez NP, called gF4 NP, or F4 + empty Gantrez NP, called F4 + gNP, and intragastrically infected with F4+ ETEC. The adjuvant effect of Gantrez®AN nanoparticles on oral vaccination of pigs and mice with F4 fimbriae is strongly influenced by polymer degradation

Mapping the geometry of the F4 group

In this paper we present a construction of the compact form of the exceptional Lie group F4 by exponentiating the corresponding Lie algebra f4. We realize F4 as the automorphisms group of the exceptional Jordan algebra, whose elements are 3 x 3 hermitian matrices with octonionic entries. We use a parametrization which generalizes the Euler angles for SU(2) and is based on the fibration of F4 via a Spin(9) subgroup as a fiber. This technique allows us to determine an explicit expression for the Haar invariant measure on the F4 group manifold. Apart from shedding light on the structure of F4 and its coset manifold OP2=F4/Spin(9), the octonionic projective plane, these results are a prerequisite for the study of E6, of which F4 is a (maximal) subgroup.Comment: 50 pages; some typos correcte

Vaccination against ETEC in pigs

Enterotoxigenic Escherichia coli (ETEC) that bear F4 fimbriae on their surface (F4+ ETEC) are a major cause of postweaning diarrhoea (PWD) in pigs. The F4 fimbriae enable the bacteria to colonize the small intestine and subsequently, to produce enterotoxins causing diarrhoea. Consequently, an F4-specific secretory IgA response at the intestinal mucosa that neutralizes the fimbriae is desired for protection against postweaning diarrhoea

Enterotoxigenic Escherichia coli induce pro-inflammatory responses in porcine intestinal epithelial cells

F4+ enterotoxigenic Escherichia coli (ETEC) cause severe diarrhoea in both neonatal and weaning piglets, resulting in morbidity and mortality. F4 fimbriae are a key virulence factor involved in the attachment of F4+ ETEC to the intestinal epithelium. Intestinal epithelial cells (IEC) are recently being recognized as important regulators of the intestinal immune system through the secretion of cytokines, however, data on how F4+ ETEC affect this cytokine secretion are scarce. By using ETEC strains expressing either polymeric, monomeric or F4 fimbriae with a reduced polymeric stability, we demonstrated that polymeric fimbriae are essential for the adhesion of ETEC to porcine IEC as well as for the secretion of IL-6 and IL-8 by ETEC-stimulated intestinal epithelial cells. Remarkably, this cytokine secretion was not abrogated following stimulation with an F4-negative strain. As this ETEC strain expresses flagellin, TLR5 mediated signalling could be involved. Indeed, porcine IEC express TLR5 and purified flagellin induced IL-6 and IL-8 secretion, indicating that, as for other pathogens, flagellin seems to be the dominant virulence factor involved in the induction of proinflammatory responses in IEC upon ETEC infection. These results indicate a potential mucosal adjuvant capacity of ETEC-derived flagellin and may improve rational vaccine design against F4+ ETEC infections

The polymeric stability of the Escherichia coli F4 (K88) fimbriae enhances its mucosal immunogenicity following oral immunization

&lt;p&gt;Only a few vaccines are commercially available against intestinal infections since the induction of a protective intestinal immune response is difficult to achieve. For instance, oral administration of most proteins results in oral tolerance instead of an antigen-specific immune response. We have shown before that as a result of oral immunization of piglets with F4 fimbriae purified from pathogenic enterotoxigenic Escherichia coli (ETEC), the fimbriae bind to the F4 receptor (F4R) in the intestine and induce a protective F4-specific immune response. F4 fimbriae are very stable polymeric structures composed of some minor subunits and a major subunit FaeG that is also the fimbrial adhesin. In the present study, the mutagenesis experiments identified FaeG amino acids 97 (N to K) and 201 (I to V) as determinants for F4 polymeric stability. The interaction between the FaeG subunits in mutant F4 fimbriae is reduced but both mutant and wild type fimbriae behaved identically in F4R binding and showed equal stability in the gastro-intestinal lumen. Oral immunization experiments indicated that a higher degree of polymerisation of the fimbriae in the intestine was correlated with a better F4-specific mucosal immunogenicity. These data suggest that the mucosal immunogenicity of soluble virulence factors can be increased by the construction of stable polymeric structures and therefore help in the development of effective mucosal vaccines.&lt;/p&gt;</p

Further steps of hepatic stimulatory substance purification

The hepatic stimulatory substance (HSS) extracted from weanling rat livers was purified 381,000-fold using chromatographic techniques including nondissociating polyacrylamide gel electrophoresis (nondenaturing PAGE). The activity of this highly purified HSS, named Acr-F4, was assessed in two in vivo models. In 40% hepatectomized rats, it produced a fivefold increase in the proliferative rate normally seen following this partial hepatectomy. In Eck fistula dogs, the level of base increase in hepatocyte renewal was amplified threefold by an infusion of Acr-F4 (50 ng/kg/day). Acr-F4 had no influence on the regenerative response of the kidney following a unilateral nephrectomy or of the bowel following a 40% resection of the small bowel. On the basis of these findings, it can be concluded that HSS (Acr-F4) has a high biological activity and is organ specific. © 1991 Plenum Publishing Corporation

Brauer algebra of type F4

We present an algebra related to the Coxeter group of type F4 which can be viewed as the Brauer algebra of type F4 and is obtained as a subalgebra of the Brauer algebra of type E6. We also describe some properties of this algebra