Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs

Peptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery ve...

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Main Authors: Sreerupa Challa, Steven M. Szczepanek, Debra Rood, Roger W. Barrette, Lawrence K. Silbart
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Advances in Virology
Online Access:http://dx.doi.org/10.1155/2011/713769
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author Sreerupa Challa
Steven M. Szczepanek
Debra Rood
Roger W. Barrette
Lawrence K. Silbart
author_facet Sreerupa Challa
Steven M. Szczepanek
Debra Rood
Roger W. Barrette
Lawrence K. Silbart
author_sort Sreerupa Challa
collection DOAJ
description Peptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. In the current study, two different carrier/adjuvant approaches were used to augment mucosal immunity to the FMDV O1 BFS G-H loop epitope, in which the G-H loop was genetically coupled to the E. coli LT-B subunit and coexpressed with the LTA2 fragment (LTA2B-GH), or the nontoxic pseudomonas exotoxin A (ntPE) was fused to LTA2B-GH at LT-A2 to enhance receptor targeting. Only guinea pigs that were inoculated intranasally with ntPE-LTA2B-GH and LTA2B-GH induced significant anti-G-H loop IgA antibodies in nasal washes at weeks 4 and 6 when compared to ovalbumin or G-H loop immunized animals. These were also the only groups that exhibited G-H loop-specific antigen-secreting cells in the nasal mucosa. These data demonstrate that fusion of nonreplicating antigens to LTA2B and ntPE-LTA2B has the potential to be used as carriers/adjuvants to induce mucosal immune responses against infectious diseases.
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spelling doaj-art-7cfac6e7ae52459c82c9b0b1c59552e92025-02-03T01:25:24ZengWileyAdvances in Virology1687-86391687-86472011-01-01201110.1155/2011/713769713769Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea PigsSreerupa Challa0Steven M. Szczepanek1Debra Rood2Roger W. Barrette3Lawrence K. Silbart4Department of Animal Science, University of Connecticut, Storrs, CT 06269, USACenter of Excellence for Vaccine Research, University of Connecticut, Storrs, CT 06269-2191, USACenter of Excellence for Vaccine Research, University of Connecticut, Storrs, CT 06269-2191, USADepartment of Animal Science, University of Connecticut, Storrs, CT 06269, USACenter of Excellence for Vaccine Research, University of Connecticut, Storrs, CT 06269-2191, USAPeptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. In the current study, two different carrier/adjuvant approaches were used to augment mucosal immunity to the FMDV O1 BFS G-H loop epitope, in which the G-H loop was genetically coupled to the E. coli LT-B subunit and coexpressed with the LTA2 fragment (LTA2B-GH), or the nontoxic pseudomonas exotoxin A (ntPE) was fused to LTA2B-GH at LT-A2 to enhance receptor targeting. Only guinea pigs that were inoculated intranasally with ntPE-LTA2B-GH and LTA2B-GH induced significant anti-G-H loop IgA antibodies in nasal washes at weeks 4 and 6 when compared to ovalbumin or G-H loop immunized animals. These were also the only groups that exhibited G-H loop-specific antigen-secreting cells in the nasal mucosa. These data demonstrate that fusion of nonreplicating antigens to LTA2B and ntPE-LTA2B has the potential to be used as carriers/adjuvants to induce mucosal immune responses against infectious diseases.http://dx.doi.org/10.1155/2011/713769
spellingShingle Sreerupa Challa
Steven M. Szczepanek
Debra Rood
Roger W. Barrette
Lawrence K. Silbart
Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs
Advances in Virology
title Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs
title_full Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs
title_fullStr Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs
title_full_unstemmed Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs
title_short Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs
title_sort bacterial toxin fusion proteins elicit mucosal immunity against a foot and mouth disease virus antigen when administered intranasally to guinea pigs
url http://dx.doi.org/10.1155/2011/713769
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