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bioRxiv · 10.1101/2020.10.01.323105

Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity

Quan, D. H.·Counoupas, C.·Nagalingam, G.·Pinto, R.·Petrovsky, N.·Britton, W. J.·Triccas, J. A.
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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 {delta}-inulin (Advax). Advax formulated with CpG oligonucleotide and the QS-21 saponin (AdvaxCpQS) was the most effective combination, demonstrated by the capacity of CysVac2/AdvaxCpQS to significantly reduce the bacterial burden in the lungs of M. tuberculosis-infected mice. CysVac2/AdvaxCpQS protection was associated with rapid influx of neutrophils, macrophages and monocytes to the site of vaccination and the induction of antigen-specific IFN-{gamma}+/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), AdvaxCpQS 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/ AdvaxCpQS 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. HighlightsO_LIAdvax adjuvant formulations improve pulmonary protection against aerosol Mycobacterium tuberculosis infection C_LIO_LIDifferent combinations of adjuvant components markedly influence the level of protection observed C_LIO_LIProtection is associated with the rapid influx of myeloid cells to the site of vaccination and the induction of antigen-specific polyfunctional CD4+ T cells in the lung. C_LIO_LIAdvax formulations abrogate vaccine-site ulceration and inflammatory cytokine production C_LI

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Quan, D. H., Counoupas, C., Nagalingam, G., Pinto, R., Petrovsky, N., Britton, W. J., Triccas, J. A.. 2020-10-01. Advax adjuvant formulations promote protective immunity against aerosol Mycobacterium tuberculosis in the absence of deleterious inflammation and reactogenicity. https://doi.org/10.1101/2020.10.01.323105

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