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Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin

BACKGROUND: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES: We aimed at evaluating and better understanding rLTB's potential as a parenteral...

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Autores principales: da Cunha, Carlos Eduardo Pouey, Moreira, Clóvis, Rocha, Andréa da Silva Ramos, Finger, Paula Fonseca, Magalhães, Carolina Georg, Ferreira, Marcos Roberto Alves, Dellagostin, Odir Antônio, Moreira, Ângela Nunes, Conceição, Fabricio Rochedo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Instituto Oswaldo Cruz, Ministério da Saúde 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719549/
https://www.ncbi.nlm.nih.gov/pubmed/29211241
http://dx.doi.org/10.1590/0074-02760170133
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author da Cunha, Carlos Eduardo Pouey
Moreira, Clóvis
Rocha, Andréa da Silva Ramos
Finger, Paula Fonseca
Magalhães, Carolina Georg
Ferreira, Marcos Roberto Alves
Dellagostin, Odir Antônio
Moreira, Ângela Nunes
Conceição, Fabricio Rochedo
author_facet da Cunha, Carlos Eduardo Pouey
Moreira, Clóvis
Rocha, Andréa da Silva Ramos
Finger, Paula Fonseca
Magalhães, Carolina Georg
Ferreira, Marcos Roberto Alves
Dellagostin, Odir Antônio
Moreira, Ângela Nunes
Conceição, Fabricio Rochedo
author_sort da Cunha, Carlos Eduardo Pouey
collection PubMed
description BACKGROUND: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES: We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS: BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS: Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS: The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.
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spelling pubmed-57195492017-12-11 Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin da Cunha, Carlos Eduardo Pouey Moreira, Clóvis Rocha, Andréa da Silva Ramos Finger, Paula Fonseca Magalhães, Carolina Georg Ferreira, Marcos Roberto Alves Dellagostin, Odir Antônio Moreira, Ângela Nunes Conceição, Fabricio Rochedo Mem Inst Oswaldo Cruz Article BACKGROUND: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES: We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS: BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS: Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS: The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed. Instituto Oswaldo Cruz, Ministério da Saúde 2017-12 /pmc/articles/PMC5719549/ /pubmed/29211241 http://dx.doi.org/10.1590/0074-02760170133 Text en https://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
da Cunha, Carlos Eduardo Pouey
Moreira, Clóvis
Rocha, Andréa da Silva Ramos
Finger, Paula Fonseca
Magalhães, Carolina Georg
Ferreira, Marcos Roberto Alves
Dellagostin, Odir Antônio
Moreira, Ângela Nunes
Conceição, Fabricio Rochedo
Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin
title Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin
title_full Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin
title_fullStr Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin
title_full_unstemmed Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin
title_short Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin
title_sort parenteral adjuvant potential of recombinant b subunit of escherichia coli heat-labile enterotoxin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719549/
https://www.ncbi.nlm.nih.gov/pubmed/29211241
http://dx.doi.org/10.1590/0074-02760170133
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