Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.
Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in man...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3729698?pdf=render |
_version_ | 1818519427222601728 |
---|---|
author | Luciana A F Gil Carlos Eduardo P da Cunha Gustavo M S G Moreira Felipe M Salvarani Ronnie A Assis Francisco Carlos F Lobato Marcelo Mendonça Odir A Dellagostin Fabricio R Conceição |
author_facet | Luciana A F Gil Carlos Eduardo P da Cunha Gustavo M S G Moreira Felipe M Salvarani Ronnie A Assis Francisco Carlos F Lobato Marcelo Mendonça Odir A Dellagostin Fabricio R Conceição |
author_sort | Luciana A F Gil |
collection | DOAJ |
description | Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC) are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB), a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH)3) developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH)3 developed a protective immune response against both BoNT/C (5 IU/mL) and BoNT/D (10 IU/mL), as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH)3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle. |
first_indexed | 2024-12-11T01:24:05Z |
format | Article |
id | doaj.art-cf69405ed2bb40ce97e722b01cbd0394 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-11T01:24:05Z |
publishDate | 2013-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-cf69405ed2bb40ce97e722b01cbd03942022-12-22T01:25:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6969210.1371/journal.pone.0069692Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.Luciana A F GilCarlos Eduardo P da CunhaGustavo M S G MoreiraFelipe M SalvaraniRonnie A AssisFrancisco Carlos F LobatoMarcelo MendonçaOdir A DellagostinFabricio R ConceiçãoBovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC) are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB), a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH)3) developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH)3 developed a protective immune response against both BoNT/C (5 IU/mL) and BoNT/D (10 IU/mL), as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH)3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle.http://europepmc.org/articles/PMC3729698?pdf=render |
spellingShingle | Luciana A F Gil Carlos Eduardo P da Cunha Gustavo M S G Moreira Felipe M Salvarani Ronnie A Assis Francisco Carlos F Lobato Marcelo Mendonça Odir A Dellagostin Fabricio R Conceição Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D. PLoS ONE |
title | Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D. |
title_full | Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D. |
title_fullStr | Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D. |
title_full_unstemmed | Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D. |
title_short | Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D. |
title_sort | production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types c and d |
url | http://europepmc.org/articles/PMC3729698?pdf=render |
work_keys_str_mv | AT lucianaafgil productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT carloseduardopdacunha productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT gustavomsgmoreira productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT felipemsalvarani productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT ronnieaassis productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT franciscocarlosflobato productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT marcelomendonca productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT odiradellagostin productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd AT fabriciorconceicao productionandevaluationofarecombinantchimericvaccineagainstclostridiumbotulinumneurotoxintypescandd |