Monophosphoryl Lipid A and Poly I:C Combination Adjuvant Promoted Ovalbumin-Specific Cell Mediated Immunity in Mice Model

Ahn, So Yeon; Le, Chau Thuy Tien; Ko, Eun-Ju

SIMPLE SUMMARY: Many research groups have investigated and developed new adjuvant candidates to promote vaccine efficacy, but only few of them were licensed. A combination of toll-like receptor (TLR) agonists can be a promising vaccine adjuvant candidate by stimulating innate immune cells and inducing antigen-specific cell-mediated immunity (CMI). In this study, a monophosphoryl lipid A (MPL) and Poly I:C combination, in low doses with ovalbumin (OVA) protein, elicited strong OVA-specific antibody production and more effective memory T cell responses compared with OVA only, OVA+MPL, OVA+Poly I:C groups at the site of immunization, as well as innate immune cell recruitment and activation. This study suggests MPL+Poly I:C as a potential CMI-inducing vaccine adjuvant candidate. ABSTRACT: Induction of antigen-specific cell-mediated immunity (CMI), as well as humoral immunity, is critical for successful vaccination against various type of pathogens. Toll-like receptor (TLR) agonists have been developed as adjuvants to promote vaccine efficacy and induce appropriate immune responses. Monophosphoryl lipid A (MPL); a TLR4 agonist, and Poly I:C; a TLR3 agonist, are known as a strong immuno-stimulator which induce Th1 response. Many studies proved and compared the efficacy of each adjuvant, but no study has investigated the combination of them. Using ovalbumin protein antigen, MPL+Poly I:C combination induced more effective antigen-specific CMI response than single adjuvants. Production of inflammatory cytokines, recruitment of innate immune cells and antigen-specific CD4/CD8 memory T cell at the immunized site had been significantly enhanced by MPL+Poly I:C combination. Moreover, MPL+Poly I:C combination enhanced ovalbumin-specific serum IgG, IgG1, and IgG2c production and proliferative function of CD4 and CD8 T cells after in vitro ovalbumin peptide stimulation. Taken together, these data suggest that the combination of MPL and Poly I:C has a potency as a CMI-inducing vaccine adjuvant with synergistically increased effects.