Fig. 9. Mice were immunized with OVA/HBsAg with or without adjuvants. Mice inoculated with OVA/HBsAg. A, serum analyzed for anti-OVA IgG on the 20th day. B, serum analyzed for anti-OVA IgG on the 28th day [89].
Recently, researchers have proved SLA exhibit high thermal stability as vaccine adjuvant: after six months of storage at 4 °C and 37 °C, the adjuvant properties of blank SLA remain unchanged, and the immunogenicity of the vaccine formulations does not change for one month after binding to the antigen [90]. It means that the use of SLA could solve the problem of cold chain transport of vaccines, thereby making the vaccine more effective and stabler.
In order to improve the body’s response to antigens, SLA was used as an immune adjuvant in cancer vaccines resulting in enhancing protection from solid and metastatic tumors [86]. Ovalbumin (OVA) is entrapped within SLA given in murine, a large amount of IFN-γ production and strong CD8+ T cell response are detected, and immune cells are recruited at the injection site and the antigens are uptake to the local draining lymph nodes in against B16 melanoma tumor challenge. When entrapped the cancer self-antigen peptide, it induced similar great response.
In addition to delivery antigen alone, it also can combine with other therapeutics to improve tumor curative effect. Stark et al. tested the combination of archaeosome from Methanobrevibacter smithii(MS) with checkpoint inhibitor immunotherapies, including αCTLA-4/αPD-1/αPD-L1, and the encouraging result is that 70% of C57BL/6 mice survived beyond 100 days from the B16-OVA tumor [91]. After two years, archaeosome combine with checkpoint inhibitor was detected again [92]. The difference is that the vaccine formulation is a simple blend of SLA and OVA(SLA-OVA). The research shows that tumor grows slower with SLA–OVA, a mass of CD45+ T cell and CD8+ T cell gather around the dying or dead tumor cells and exist in the survived tumor tissues widely. Furthermore, immunohistochemical tests demonstrated that most of tumor mass was consisted of dead cells.
Whether adjuvants and antigens are co-encapsulated in liposomes (SLA-Enc) or simply mixed with antigen-containing liposomes (SLA-Adm) affect the intensity and quality of T cell-induced reactions are related to the type of adjuvants. In terms of simply admixed SLA with antigen, the way of entrapped cargo may induce a high antigen loss during preparation, while a study has revealed that this new formulation can obtain similar induction of robust adjuvant activity as an encapsulated formulation deliver encapsulated antigen with SLA and without antigen loss during production. The new formulation may lead to excellent reproducibility, while compared to the encapsulation, the mixed formula shows negative energy to induce antigen CD8+ T cell to activate dendritic cells in vitro , and the mixed formula retains ovarian injection for 24 h, but the encapsulated formulation maintains it for 48 h in vitro (Fig. 10) [92]. SLA has become a new attractive role as effective adjuvant, the advantages of two formulation are of great significance in a cancer vaccine, so proposing a new formulation with no antigen loss, and better immune stimulation, is a key that researchers need to tackle in the future.