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.