Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 18, Issue 5, Pages 1222-1234Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-021-00669-w
Keywords
Manganese (Mn2+); adjuvant; cGAS-STING; NLRP3; antigen presentation
Categories
Funding
- National Natural Science Foundation of China [31830022, 81621001]
- Chinese Ministry of Science and Technology [2019YFA0508500]
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The colloidal manganese salt (Mn jelly, MnJ) acts as both an immune potentiator and a delivery system, promoting immune responses by inducing antibody production and CD4(+)/CD8(+) T-cell proliferation and activation. It also shows promise as a mucosal adjuvant, inducing high levels of secretory IgA and proving effective for various antigens, making it a potential candidate for adjuvant use.
Aluminum-containing adjuvants have been used for nearly 100 years to enhance immune responses in billions of doses of vaccines. To date, only a few adjuvants have been approved for use in humans, among which aluminum-containing adjuvants are the only ones widely used. However, the medical need for potent and safe adjuvants is currently continuously increasing, especially those triggering cellular immune responses for cytotoxic T lymphocyte activation, which are urgently needed for the development of efficient virus and cancer vaccines. Manganese is an essential micronutrient required for diverse biological activities, but its functions in immunity remain undefined. We previously reported that Mn2+ is important in the host defense against cytosolic dsDNA by facilitating cGAS-STING activation and that Mn2+ alone directly activates cGAS independent of dsDNA, leading to an unconventional catalytic synthesis of 2 ' 3 '-cGAMP. Herein, we found that Mn2+ strongly promoted immune responses by facilitating antigen uptake, presentation, and germinal center formation via both cGAS-STING and NLRP3 activation. Accordingly, a colloidal manganese salt (Mn jelly, MnJ) was formulated to act not only as an immune potentiator but also as a delivery system to stimulate humoral and cellular immune responses, inducing antibody production and CD4(+)/CD8(+) T-cell proliferation and activation by either intramuscular or intranasal immunization. When administered intranasally, MnJ also worked as a mucosal adjuvant, inducing high levels of secretory IgA. MnJ showed good adjuvant effects for all tested antigens, including T cell-dependent and T cell-independent antigens, such as bacterial capsular polysaccharides, thus indicating that it is a promising adjuvant candidate.
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