Oral immunization of mice with attenuated Salmonella enteritidis containing a recombinant plasmid which codes for production of the B subunit of heat-labile Escherichia coli enterotoxin

Abstract

We used Salmonella enteritidis serotype dublin strain SL1438, a nonreverting, aromatic-dependent, histidine-requiring mutant, as a recipient for a recombinant plasmid coding for production of the nontoxic B subunit of the heat-labile Escherichia coli enterotoxin. The S. enteritidis derivative EL23 produced heat-labile enterotoxin subunit B that was indistinguishable from heat-labile enterotoxin subunit B produced by strains of E. coli or Salmonella typhi harboring the same plasmid. Mice immunized orally with strain EL23 developed progressively increasing mucosal and serum antibody responses to both heat-labile enterotoxin subunit B and to the lipopolysaccharide of the vaccine strain. The mucosal antibody response was shown to be immunoglobulin A specific and to be capable of neutralizing the biological activities of both E. coli heat-labile enterotoxin and cholera enterotoxin in vitro.

In vivo treatment with anti‐interleukin‐13 antibodies significantly reduces the humoral immune response against an oral immunogen in mice

“…Unlike most antigens given orally, administration of LT-B in this manner results in the formation of a significant intestinal antibody response. 25 Furthermore, following administration of this antigen, we found that IL-13 mRNA expression in the mesenteric lymph 5). Twenty hours after administration, RNA was extracted from the mesenteric lymph nodes of each animal; 200 ng of poly A + RNA were reverse transcribed, and then 20% of each cDNA was amplified by PCR using primers specific for IL-12p40 (a), IL-13 (b) or glyceraldehyde 3-phosphate dehydrogenase (G3PDH) (c).…”

“…Mice were killed 21 days following primary immunization with LT-B or 10 days following secondary immunization with LT-B and sera and mucosal samples were taken. Intestinal samples containing IgA were obtained as previously described 25 by homogenization (Tissuemizer, Tekmar, Cincinnati, OH) of the small intestines in 50 mM EDTA containing 0 . 1 mg soybean trypsin inhibitor.…”

“…We have previously demonstrated that secondary mucosal anti-LT-B responses occur following multiple oral exposures to LT-B. 25 We took advantage of this fact to investigate the effect anti-Leu-IL-13 antibody treatment had on such a secondary response. Groups of BALB/c mice were orally administered LT-B 21 days prior to receiving a second oral dose of this antigen.…”

Particulate delivery systems for vaccines: what can we expect?

“…In the same way, the diversity of strategies incorporating and exploiting both the natural and contrived characteristics of bacterial invasion and their diverse and tractable genetic features offers much potential in the generation of a vaccine delivery platform. In similar fashion to the delivery of eukaryotic expression vectors as DNA vaccines (notably with the potential for oral delivery), the use of attenuated Salmonella for delivery of a recombinant plasmid encoding for the non-toxic B subunit of E. coli LT was shown in-vivo for the purposes of vaccination by Clements et al (1986). Oral immunization of mice showed progressively increasing mucosal and serum antibody responses to both the E. coli LT subunit and the lipopolysaccharide (LPS) of the vaccine strain, together with the mucosal production of neutralizing IgA.…”

Evaluation of YadC protein delivered by live attenuatedSalmonellaas a vaccine against plague

“…Live attenuated Salmonella strains were first developed as vaccines to prevent disease caused by Salmonella infections in humans and animals (Germanier & Fuer, 1975;Stocker et al, 1983;Hassan & Curtiss, 1990). Subsequently, genetically modified attenuated Salmonella strains were constructed for delivery of heterologous antigens (Formal et al, 1981;Clements et al, 1986;Nakayama et al, 1988). Orally administered Salmonella vaccines offer a variety of advantages over traditional vaccines, including stimulation of both systemic and mucosal responses, which are important for protection against pathogens such as plague, needle-free delivery, and a relatively low cost of production .…”