Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice.
Pulmonary vaccination is a promising route for immunization against tuberculosis because the lung is the natural site of infection with Mycobacterium tuberculosis. Yet, adjuvants with a suitable safety profile need to be found to enhance mucosal immunity to recombinant antigens. The aim of this stud...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3651129?pdf=render |
| _version_ | 1818778065281482752 |
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| author | Julie Todoroff Muriel M Lemaire Catherine Fillee Fabienne Jurion Jean-Christophe Renauld Kris Huygen Rita Vanbever |
| author_facet | Julie Todoroff Muriel M Lemaire Catherine Fillee Fabienne Jurion Jean-Christophe Renauld Kris Huygen Rita Vanbever |
| author_sort | Julie Todoroff |
| collection | DOAJ |
| description | Pulmonary vaccination is a promising route for immunization against tuberculosis because the lung is the natural site of infection with Mycobacterium tuberculosis. Yet, adjuvants with a suitable safety profile need to be found to enhance mucosal immunity to recombinant antigens. The aim of this study was to evaluate the immunogenicity, the safety and the protective efficacy of a subunit vaccine composed of the immunodominant mycolyl-transferase antigen 85A (Ag85A) and one of three powerful mucosal adjuvants: the oligodeoxynucleotide containing unmethylated cytosine-phosphate-guanine motifs (CpG), the monophosphoryl lipid A of Salmonella minnesota (MPLA) or the B subunit of heat-labile enterotoxin of Escherichia coli (LTB). BALB/c mice were vaccinated in the deep lungs. Our results showed that lung administration of these adjuvants could specifically induce different types of T cell immunity. Both CpG and MPLA induced a Th-1 type immune response with significant antigen-specific IFN-γ production by spleen mononuclear cells in vitro and a tendency of increased IFN-γ in the lungs. Moreover, MPLA triggered a Th-17 response reflected by high IL-17A levels in the spleen and lungs. By contrast, LTB promoted a Th-2 biased immune response, with a production of IL-5 but not IFN-γ by spleen mononuclear cells in vitro. CpG did not induce inflammation in the lungs while LTB and MPLA showed a transient inflammation including a neutrophil influx one day after pulmonary administration. Pulmonary vaccination with Ag85A without or with MPLA or LTB tended to decrease bacterial counts in the spleen and lungs following a virulent challenge with M. tuberculosis H37Rv. In conclusion, CpG and MPLA were found to be potential adjuvants for pulmonary vaccination against tuberculosis, providing Th-1 and Th-17 immune responses and a good safety profile. |
| first_indexed | 2024-12-18T11:38:48Z |
| format | Article |
| id | doaj.art-dcaab0b2e022487d97a58d6fb85c8530 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T11:38:48Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dcaab0b2e022487d97a58d6fb85c85302022-12-21T21:09:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6334410.1371/journal.pone.0063344Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice.Julie TodoroffMuriel M LemaireCatherine FilleeFabienne JurionJean-Christophe RenauldKris HuygenRita VanbeverPulmonary vaccination is a promising route for immunization against tuberculosis because the lung is the natural site of infection with Mycobacterium tuberculosis. Yet, adjuvants with a suitable safety profile need to be found to enhance mucosal immunity to recombinant antigens. The aim of this study was to evaluate the immunogenicity, the safety and the protective efficacy of a subunit vaccine composed of the immunodominant mycolyl-transferase antigen 85A (Ag85A) and one of three powerful mucosal adjuvants: the oligodeoxynucleotide containing unmethylated cytosine-phosphate-guanine motifs (CpG), the monophosphoryl lipid A of Salmonella minnesota (MPLA) or the B subunit of heat-labile enterotoxin of Escherichia coli (LTB). BALB/c mice were vaccinated in the deep lungs. Our results showed that lung administration of these adjuvants could specifically induce different types of T cell immunity. Both CpG and MPLA induced a Th-1 type immune response with significant antigen-specific IFN-γ production by spleen mononuclear cells in vitro and a tendency of increased IFN-γ in the lungs. Moreover, MPLA triggered a Th-17 response reflected by high IL-17A levels in the spleen and lungs. By contrast, LTB promoted a Th-2 biased immune response, with a production of IL-5 but not IFN-γ by spleen mononuclear cells in vitro. CpG did not induce inflammation in the lungs while LTB and MPLA showed a transient inflammation including a neutrophil influx one day after pulmonary administration. Pulmonary vaccination with Ag85A without or with MPLA or LTB tended to decrease bacterial counts in the spleen and lungs following a virulent challenge with M. tuberculosis H37Rv. In conclusion, CpG and MPLA were found to be potential adjuvants for pulmonary vaccination against tuberculosis, providing Th-1 and Th-17 immune responses and a good safety profile.http://europepmc.org/articles/PMC3651129?pdf=render |
| spellingShingle | Julie Todoroff Muriel M Lemaire Catherine Fillee Fabienne Jurion Jean-Christophe Renauld Kris Huygen Rita Vanbever Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice. PLoS ONE |
| title | Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice. |
| title_full | Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice. |
| title_fullStr | Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice. |
| title_full_unstemmed | Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice. |
| title_short | Mucosal and systemic immune responses to Mycobacterium tuberculosis antigen 85A following its co-delivery with CpG, MPLA or LTB to the lungs in mice. |
| title_sort | mucosal and systemic immune responses to mycobacterium tuberculosis antigen 85a following its co delivery with cpg mpla or ltb to the lungs in mice |
| url | http://europepmc.org/articles/PMC3651129?pdf=render |
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