The Manganese Salt (MnJ) Functions as A Potent Universal Adjuvant

Abstract

15Aluminum adjuvants have been used for a century in various vaccines due to its ability to 16 potentiate humoral immunity and safety records since 1920s. Manganese is an essential 17 micronutrient required for diverse biological activities in cells. We previously found that Mn 2+ is a 18 strong type I-interferon stimulator activating the cGAS-STING pathway. Herein we report that a 19 colloidal manganese salt (MnJ) is a potent adjuvant to induce both humoral and cellular immune 20 responses, particularly CTL activation. When administrated intranasally, MnJ was also a strong 21 mucosal adjuvant, inducing high levels of IgA antibodies. MnJ strongly promoted dendritic cell 22 maturation and antigen-specific T cell activation. Interestingly, IL-1/-18 induction and release by 23Mn 2+ -activated ASC-mediated inflammasomes were not observed. MnJ showed great adjuvant 24 effects to all tested antigens including inactivated viruses, recombinant proteins and peptides by 25 either intramuscular or intranasal immunization. These findings may have implications in 26 developing potent but safe Mn 2+ -containing vaccines. 27

Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

“…The peptides were synthesized and coupled to KLH through SMCC (Thermo Fisher Scientific, MA, USA) by GL Biochem Ltd. (Shanghai, China). For each peptide, three female mice (BALB/c) approximately 6~8 weeks old were immunized four times on a weekly schedule, and 50 mg KLH conjugated peptide was mixed with 60 mg manganese salt (MnJ) adjuvants (Zhang et al, 2019) for each immunization through intraperitoneal (IP) injections. Serum samples were collected 7 d after each immunization for microarray and neutralization assays.…”

Chitosan-Poly(Acrylic Acid) Nanoparticles Loaded with R848 and MnCl2 Inhibit Melanoma via Regulating Macrophage Polarization and Dendritic Cell Maturation

“…24,25 Recently, a new type of nano-Mn compound adjuvant has been developed for activating humoral, cellular, and mucosal immunity, especially the cytotoxic T cell-mediated immune response. 26,27 However, excess exposure to Mn 2+ can cause cognitive impairment. 28 The delivery of Mn 2+ with NPs may help in its controlled release, thereby reducing neurotoxicity.…”

A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge

“…We also conducted studies on how the immunogenicity of K562-S was impacted by coadministration with specific adjuvants, including Alum, MnJ and CpG, individually and in combination. MnJ is a novel adjuvant derived from the discovery that Mn2+ is a potent inducer of type I interferons by activating cGAS-STING pathway, and was evidenced recently for its capability to stimulate CD4+/CD8+ T-cell proliferation, indicating a potential to facilitate antibody production [30][31][32]. Consequently, we identified a dual-component adjuvant, CpG plus Alum or MnJ, as an effective adjuvant to augment the antibody response elicited by K562-S while driving the response toward a Th1/Th2 balance.…”