PPD in HBsAg vaccine formulation suppressed IFN-γ and IL-4 cytokine responses and induced long-lived humoral immune responses: Results from 220-day monitoring of specific IgG responses.

Abstract

Here, immune responsesand long-lived IgG responses of HBsAg-Alum, HBsAg-MF59, as well as HBsAg-MF59 were compared when formulated with PPD. BALB/cmice were vaccinatedsubcutaneously three times withatwo-week-interval. Then, specific IgG, long-lived IgG responses up to 220 days,andIgG1/IgG2aisotypes,andIFN-γ and IL-4 on spleen cell culture supernatant were assessed using ELISA. IFN-γ cytokine response between MF59- and Alum-adjuvanted vaccines did not show a significant difference. HBsAg-Alum revealed an increase in IL-4 cytokineversus HBsAg-MF59 at borderline(P=0.0553).In addition, HBsAg-MF59+PPD 10 µg showed a significant decrease in IL-4 and IFN-γ cytokinesversusHBsAg-MF59. Furthermore, HBsAg-MF59+PPD10 µg showed a significant increase intheIL-2/IL-4 ratioversusHBsAg-MF59 (P=0.0339).Specific IgG antibody showed a significant increase in HBsAg-MF59, as compared with HBsAg-Alum. Furthermore, HBsAg-MF59 plus PPD showed a significant increase in IgG responsesversusHBsAg-MF59 and HBsAg-Alum groups. Long-lived IgGresponses showeda significant increase in HBsAgMF59 versus HBsAg-Alum group and PPD in the HBsAg-MF59 vaccine formulation, resulting in a significant increase in IgG responses versus HBsAg-MF59 group. In addition,HBsAg-MF59 plus PPDsuppressed IgG1 response versus HBsAg-Alum. However, HBsAg-MF59 showed a significant increase in IgG2α versustheHBsAg-Alum group (P=0.0190). Immunization with HBsAg-MF59+PPD (10 µg) showed a significant increase versustheHBsAg-MF59 group (P=0.0040).IgG2a/IgG1 ratioinHBsAg-MF59+PPD1µgandHBsAg-MF59+PPD10 µggroups showed a significant increaseversusHBsAg-MF59 groups(P<0.0345). PPD leads toamore potent long-lived IgG responses intheHBsAg vaccine, highlighting its potentialasa component of a complex adjuvant.