Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection
Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion protein...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-12-01
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| Series: | Human Vaccines & Immunotherapeutics |
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| Online Access: | http://dx.doi.org/10.1080/21645515.2017.1368598 |
| _version_ | 1827809972532019200 |
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| author | Bruno de Paula Oliveira Santos Monalisa Martins Trentini Renato Beilner Machado Mara Rúbia Nunes Celes André Kipnis Nikolai Petrovsky Ana Paula Junqueira-Kipnis |
| author_facet | Bruno de Paula Oliveira Santos Monalisa Martins Trentini Renato Beilner Machado Mara Rúbia Nunes Celes André Kipnis Nikolai Petrovsky Ana Paula Junqueira-Kipnis |
| author_sort | Bruno de Paula Oliveira Santos |
| collection | DOAJ |
| description | Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMX formulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. BALB/c mice were immunized three times intramuscularly with these vaccine formulations. Injection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b+) in the draining lymph nodes consistent with a chemotactic adjuvant effect. Advax4+CMX and Advax4+ECMX induced the highest levels of IgG1 and IgG2a antibodies against rCMX and rECMX, respectively. Immunized mice challenged with Mycobacterium tuberculosis (Mtb) had increased vaccine-specific Th1 responses in the lungs together with reduced Mtb – associated alveolar damage, although only the Advax4+ECMX vaccine demonstrated significant reduction of lung bacterial load. This study confirmed Advax4+ECMX as a potential TB vaccine candidate, with potential for further optimization and clinical development. |
| first_indexed | 2024-03-11T22:47:15Z |
| format | Article |
| id | doaj.art-cff861ef613e4da4bdf6d259f236811e |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:47:15Z |
| publishDate | 2017-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-cff861ef613e4da4bdf6d259f236811e2023-09-22T08:17:52ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2017-12-0113122967297610.1080/21645515.2017.13685981368598Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infectionBruno de Paula Oliveira Santos0Monalisa Martins Trentini1Renato Beilner Machado2Mara Rúbia Nunes Celes3André Kipnis4Nikolai Petrovsky5Ana Paula Junqueira-Kipnis6Federal University of GoiásFederal University of GoiásFederal University of GoiásFederal University of GoiásFederal University of GoiásFlinders University and Vaxine Pty Ltd, Flinders Medical CenterFederal University of GoiásTuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMX formulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. BALB/c mice were immunized three times intramuscularly with these vaccine formulations. Injection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b+) in the draining lymph nodes consistent with a chemotactic adjuvant effect. Advax4+CMX and Advax4+ECMX induced the highest levels of IgG1 and IgG2a antibodies against rCMX and rECMX, respectively. Immunized mice challenged with Mycobacterium tuberculosis (Mtb) had increased vaccine-specific Th1 responses in the lungs together with reduced Mtb – associated alveolar damage, although only the Advax4+ECMX vaccine demonstrated significant reduction of lung bacterial load. This study confirmed Advax4+ECMX as a potential TB vaccine candidate, with potential for further optimization and clinical development.http://dx.doi.org/10.1080/21645515.2017.1368598tuberculosisvaccineadjuvanttbecmxadvaxdelta inulin |
| spellingShingle | Bruno de Paula Oliveira Santos Monalisa Martins Trentini Renato Beilner Machado Mara Rúbia Nunes Celes André Kipnis Nikolai Petrovsky Ana Paula Junqueira-Kipnis Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection Human Vaccines & Immunotherapeutics tuberculosis vaccine adjuvant tb ecmx advax delta inulin |
| title | Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection |
| title_full | Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection |
| title_fullStr | Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection |
| title_full_unstemmed | Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection |
| title_short | Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection |
| title_sort | advax4 delta inulin combination adjuvant together with ecmx a fusion construct of four protective mtb antigens induces a potent th1 immune response and protects mice against mycobacterium tuberculosis infection |
| topic | tuberculosis vaccine adjuvant tb ecmx advax delta inulin |
| url | http://dx.doi.org/10.1080/21645515.2017.1368598 |
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