Preclinical evaluation of microencapsulated CFA/II oral vaccine against enterotoxigenic E. coli

Reid, Robert H.; Boedeker, Edgar C.; McQueen, C.; Davis, Dorothy Salisbury; Tseng, Li-Yun; Kodak, James; Sau, Keya; Wilhelmsen, Catherine L.; Nellore, Ranjani; Dalal, Poonam; Bhagat, Hitesh R.

doi:10.1016/0264-410x(93)90013-n

Cited by 45 publications

(12 citation statements)

References 9 publications

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“…This was largely influenced by the costimulation of CFA/I-specific Th2 cells. The effectiveness of this vaccine also is apparent when compared with past unsuccessful attempts to elicit mucosal IgA Abs with an attenuated E. coli-CFA/I construct in conjunction with cholera toxin (25), despite repeated oral doses as others have shown (47)(48)(49). However, the unexpected finding from this study was the impaired S-IgA anti-CFA/I responses by L-Sel Ϫ/Ϫ mice while systemic IgA responses remained unabated.…”

Section: Discussionmentioning

confidence: 54%

Impaired Mucosal Immunity in L-Selectin-Deficient Mice Orally Immunized with aSalmonellaVaccine Vector

Pascual

White

Larson

et al. 2001

The Journal of Immunology

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Lymphocyte trafficking in the gastrointestinal tract is primarily mediated by interactions with the mucosal addressin cell adhesion molecule 1 and its lymphocyte ligand, α4β7, and partly by L-selectin (L-Sel) interactions with peripheral node addressin coexpressed on some mucosal addressin cell adhesion molecule 1. We inquired whether intestinal responses in mice lacking L-Sel would be enhanced. L-Sel-deficient (L-Sel−/−) mice were orally immunized with either Salmonella vaccine vector or Salmonella vector-expressing colonization factor Ag I (CFA/I) from enterotoxigenic Escherichia coli. In L-Sel−/− mice, mucosal IgA anti-CFA/I fimbrial responses were greatly reduced, and systemic IgG2a anti-CFA/I fimbrial responses were 26-fold greater compared with C57BL/6 (L-Sel+/+) mice. L-Sel−/− Peyer’s patch (PP) CD4+ Th cells revealed IFN-γ-dominated responses and an unprecedented absence of IL-4, whereas the expected mixed Th cell phenotype developed in L-Sel+/+ mice. PP CD4+ Th cell anti-Salmonella responses were nearly nonexistent in L-Sel−/− mice immunized with either Salmonella vaccine. Splenic CD4+ Th cell anti-Salmonella responses were reduced but did show cytokine production in Ag restimulation assays. Increased colonization of PP and spleen was noted only with the Salmonella vector in L-Sel−/− mice, resulting in increased splenomegaly, suggesting that the Salmonella-CFA/I vaccine was not as infectious or that the presence of the fimbriae improved clearance, possibly because of reduced neutrophil recruitment. However, sufficient anti-Salmonella immunity was induced, because Salmonella vector-immunized L-Sel−/− mice showed complete protection against wild-type Salmonella challenge, unlike L-Sel+/+ mice. This evidence shows that L-Sel is important for development of mucosal immunity, and absence of L-Sel is protective against salmonellosis.

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Section: Discussionmentioning

confidence: 54%

Impaired Mucosal Immunity in L-Selectin-Deficient Mice Orally Immunized with aSalmonellaVaccine Vector

Pascual

White

Larson

et al. 2001

The Journal of Immunology

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“…Nasally administered pharmaceuticals generally are not required to be sterile; however, sterilization may be necessary for nasal particulate vaccine formulations because of the propensity of particulate formulations to be taken up by M‐cells present in the NALT. Sterilization may be achieved by using aseptic processing under GMP conditions throughout formulation and/or use of nonthermal methods of terminal sterilization such as gamma radiation and filtration 238, 239. Another important concern related to delivery systems for nasal vaccination is carrier and vaccine stability during production and storage.…”

Section: Industrial and Regulatory Aspectsmentioning

confidence: 99%

Pharmaceutical Aspects of Intranasal Delivery of Vaccines Using Particulate Systems

Sharma

Mukkur

Benson

et al. 2009

Journal of Pharmaceutical Sciences

146

137

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“…To protect against the antigen-altering properties of the gastrointestinal tract, purified fimbriae are microencapsulated for intragastric immunization of rabbits (12), but only minimal serum and secretory IgA responses are induced. However, direct immunization of microencapsulated fimbria into rabbit duodenum does improve fimbria-specific Peyer's patch and splenic B-cell responses (40). These studies indicate that ETEC fimbriae must be sufficiently protected to withstand the host's gastrointestinal tract.…”

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confidence: 88%

Partially Assembled K99 Fimbriae Are Required for Protection

et al. 2005

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Antibodies to K99 fimbriae afford protection to F5؉ bovine enterotoxigenic Escherichia coli (ETEC). Previous studies show that murine dams immunized with Salmonella vaccine vectors stably expressing K99 fimbriae confer protection to ETEC-challenged neonatal pups. To begin to address adaptation of the K99 scaffold to display heterologous B-and T-cell epitopes, studies were conducted to determine how much of the assembled K99 fimbria is required to maintain protective immunity. Sequential deletions in the K99 gene clusters were made, resulting in diminished localization of the K99 fimbrial subunit in the outer membrane. As placement of the K99 fimbrial subunit became progressively contained within the vaccine vector, diminished immunoglobulin A (IgA) and IgG1 antibody titers, as well as diminished Th2-type cytokine responses, were observed in orally immunized mice. Deletion of fanGH, which greatly reduced the export of the fimbrial subunit to the outer membrane, showed only partial reduction in protective immunity. By contrast, deletion of fanDEFGH, which also reduced the export of the fimbrial subunit to the outer membrane but retained more subunit in the cytoplasm, resulted in protective immunity being dramatically reduced. Thus, these studies showed that retention of K99 fimbrial subunit as native fimbriae or with the deletion of fanGH is sufficient to confer protection.

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Preclinical evaluation of microencapsulated CFA/II oral vaccine against enterotoxigenic E. coli

Cited by 45 publications

References 9 publications

Impaired Mucosal Immunity in L-Selectin-Deficient Mice Orally Immunized with aSalmonellaVaccine Vector

Impaired Mucosal Immunity in L-Selectin-Deficient Mice Orally Immunized with aSalmonellaVaccine Vector

Pharmaceutical Aspects of Intranasal Delivery of Vaccines Using Particulate Systems

Partially Assembled K99 Fimbriae Are Required for Protection

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