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

Resumo

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.

Descrição

Palavras-chave

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.