Evaluation of alum-based adjuvant on the immunogenicity of salmonella enterica serovar typhi conjugates vaccines

Abstract

The function of adjuvant in maintaining the long-term immune response to Typhoid conjugate vaccine (TCV) was evaluated in. Two TCV products, Vi-DT and Vi-TT, were formulated in either aluminum phosphate (AlPO₄) or aluminum hydroxide (AlOH) as adjuvants and TCV formulated in phosphate buffer saline were used as controls. In each case, a group of Balb/c mice was injected intramuscularly with two doses of the formulated vaccine at two-week intervals. The anti-Vi IgG responses were monitored by Enzyme-Linked Immunosorbent Assay and the levels of CD4⁺ T-cells expressing cytokine were characterized using intracellular cytokine staining. All mice immunized by TCV formulated in adjuvant elicited anti-Vi response to a higher level than the group receiving TCV formulated in PBS. The extent of adsorption of TCV in AlOH was greater than that in AlPO₄, and this finding correlated well with the observation that the mice immunized with two doses of Vi-DT(AlOH) elicited anti-Vi IgG to a level higher than that seen with Vi-DT(AlPO₄). The mice primed with Vi-TT(AlOH) produced lower anti-Vi IgG (25.901 GM) compared to those receiving Vi-TT(AlPO₄) (49.219 GM). However, after the second injection, the former raised the antibody level significantly to 137.008 GM while the latter provided a value of only 104.966 GM. The groups of mice vaccinated by TCV formulated in AlOH expressed IL4 at higher levels than the other groups, which correlated positively with the high Anti-Vi IgG in these animals. In conclusion, AlOH could be recommended as an effective adjuvant for TCV to provide a long-term immune response.

Keywords: Typhoid conjugate vaccine; Vi; adjuvant; anti-Vi IgG; cytokine; diphteria toxoid; tetanus toxoid.