AI Article Synopsis
- - The study focuses on developing safe and effective adjuvants for vaccines, particularly using δ-inulin (Advax) which showed promising results against Mycobacterium tuberculosis in mice.
- - The combination of CysVac2 with Advax and other immune boosters significantly reduced bacterial presence in the lungs and enhanced immune cell activity, especially CD4 T cells.
- - Advax was found to provide protection similar to other potent adjuvants without causing high inflammatory responses or side effects, suggesting its potential for safe human vaccine applications.
Article Abstract
The development of safe and effective adjuvants is a critical goal of vaccine development programs. In this report, we defined the immunostimulatory profile and protective effect against aerosol Mycobacterium tuberculosis infection of vaccine formulations incorporating the semi-crystalline adjuvant δ-inulin (Advax). Advax formulated with CpG oligonucleotide and the QS-21 saponin (Advax) was the most effective combination, demonstrated by the capacity of CysVac2/Advax to significantly reduce the bacterial burden in the lungs of M. tuberculosis-infected mice. CysVac2/Advax protection was associated with rapid influx of neutrophils, macrophages and monocytes to the site of vaccination and the induction of antigen-specific IFN-γ/IL-2/TNF polyfunctional CD4 T cells in the lung. When compared to the highly potent adjuvant combination of monophosphoryl lipid A and dimethyldioctadecylammonium bromide (MPL/DDA), Advax imparted a similar level of protective efficacy yet without the profound stimulation of inflammatory cytokines and vaccination site ulceration observed with MPL/DDA. Addition of DDA to CysVac2/Advax further improved the protective effect of the vaccine, which correlated with increased polyfunctional CD4 T cells in the lung but with no increase in vaccine reactogenicity. The data demonstrate that Advax formulations can decouple protective tuberculosis immunity from reactogenicity, making them ideal candidates for human application.
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| http://dx.doi.org/10.1016/j.vaccine.2021.02.041 | DOI Listing |
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