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
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2017
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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/CD11bC) in the draining lymph nodes
consistent with a chemotactic adjuvant effect. Advax4CCMX and Advax4CECMX 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
vaccine demonstrated significant reduction of lung bacterial load. This study con
Cfi
ECMX
rmed
Advax4CECMX as a potential TB vaccine candidate, with potential for further optimization and clinical
development.
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Tuberculosis, Vaccine, Adjuvant, TB, ECMX, Advax, Delta inulin
Citação
SANTOS, Bruno de Paula Oliveira et al. 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, Philadelphia , v. 13, n. 2, p. 2967-2976, 2017. DOI: 10.1080/21645515.2017.1368598. Disponível em: https://pubmed.ncbi.nlm.nih.gov/28937879/. Acesso em: 22 ago. 2024.