Table 2.
Adjuvanticity of lipid delivery.
| Antigen | Ionizable Lipid, N/P or weight ratio (if specified) | Significant Findings | Reference |
|---|---|---|---|
| SARS-CoV-2 spike (wild-type and Omicron BA.1) | SM-102 (N/P Ratio = 6) | Induced comparable or superior humoral immunity to a matched mRNA-LNP in multiple rodent models, improved protection from challenge | Liao et al. Molecular Therapy Methods & Clinical Development (36) |
| SARS-CoV-2 spike (Delta variant) fused to CD40L ectodomain | KC2 and SM-102 (N/P Ratio = 6) | Relative to naked DNA, LNP formulation led to superior neutralization titers and reduced viral loads in challenge, was dose-sparing in hamsters | Tamming et al. Molecular Therapy Methods & Clinical Development. (129) |
| Influenza H3N2 HA | MC3 (N/P ratio = 4.5) | Induced antibody titers and T cell responses in swine, with significantly reduced viral shedding and lung pathology in challenge | Nguyen et al. mSphere. (130) |
| Influenza H1N1 HA | MC3 (N/P ratio = 4.5 and 5.5) | Induced humoral and cellular responses as well as mediated protection in an influenza challenge model in mice and swine | Nguyen et al. mSphere. (130) |
| HPV16 and HPV18 E6/E7 | MC3, SM-102, and ALC-0315 | Enhanced T Cell responses relative to DNA delivered using electroporation. SM-102-based formulations drove superior immunogenicity relative to MC3 and ALC-0315. | Li et al. Vaccines. (131) |
| SARS-CoV-2 spike (Gamma variant) | Ionizable lipid not specified (Lipid to DNA weight ratio = 10:1) | Induced robust humoral and cellular immune responses, reduction in viral load, lung pathology in SARS-CoV-2 challenge models in mice and hamsters | Guimaraes et al. Nature Communications (37) |
| Influenza H1N1 HA and SARS-CoV-2 spike (wild-type) | SM-102 (N/P ratios 10.5, 5.3, and 2.6) | Robust innate immune responses, notably migratory DCs. Comparable humoral immune responses and superior T cell responses to mRNA-LNP and adjuvanted protein. Protection from challenge in SARS-CoV-2 model | Tursi et al. Cell Rep Med. (38) |
| SARS-CoV-2 spike (Omicron variant) | SM-102 (Total lipid to DNA weight ratio = 20:1) | Induced humoral immune responses and is protective in a wild-type SARS-CoV-2 challenge model in hamsters | Yang et al. Molecular Therapy Nucleic Acids. (132) |
| B. burgdorferi OspC | KC2 | Elicited binding and functional antibody responses, mediates protection in B. burgdorferi challenge | Pfeifle et al. Frontiers in Immunology. (133) |
| OX-40L | KC2, MC3, C12-200 (Ionizable lipid to DNA weight ratio 5:1) | Intratumoral delivery of plasmid DNA in LNPs led to a reduction in tumor burden. OX-40L-expressing plasmid in combination with an siRNA led to improved challenge outcomes. | Qin et al. Journal of Controlled Release. (134) |
| SARS-CoV-2 spike, PD-L1, p53R172H | SM-102, ALC-0315, MC3 | Induced superior humoral and cellular immune responses relative to electroporation. Expression of PD-L1/p53 variant led to humoral immune responses and a reduction in tumor burden | Chai et al. Molecular Cancer. (135) |