Dose-Dependent Variation of Typhi Vaccine-Induced Immunity by Bifidobacteria in a Murine Model: Implications for Probiotic Adjuvant Use

Sahar El Hadad, Ayeshah Zakareya, Ahmed Al-Hejin, Alawiah Alhebshi, Safyiah Alzahrani, Hadba Al-Amrah, Zeina Sharawi, Manal Zubair, Saeedah Aljadani, Rana Jambi and Jehan Alrahimi

Background and Objective: The potential of probiotics as adjuvants in vaccination strategies is a promising area of research, particularly with concerns for immunocompromised populations. This study investigates how different doses of bifidobacteria affect the immune response to a Salmonella typhi (S. typhi ) vaccine in mice. Materials and Methods: Forty female Swiss mice, aged six to eight weeks, were divided into four groups. These groups included a control group, a vaccine-only group and two groups that received the vaccine with either a low (10⁸ CFU) or high (10¹² CFU) dose of bifidobacteria. The immune response was measured on days 28 and 42 post-vaccination, focusing on mucosal gene expression and immunoglobulin levels. Statistical tests, including One-way ANOVA, were performed on all groups, with statistical significance determined by p<0.05. Results: The study found that bifidobacteria modulate immunity dose-dependently, reducing mucosal TLR2 expression and suppressing cytokines IFN-γ, IL-4 and IL-10, with higher doses enhancing vaccine efficacy. Serum antibody analysis showed increased IgG, IgM and IgA, with a dose-response effect for IgA but not IgG. By day 42, bifidobacteria sustained IgG and IgM levels but did not further elevate IgA beyond vaccine-induced levels. Conclusion: This study underscores the efficacy of lower Bifidobacterium doses in boosting immune regulation, highlighting the crucial need for stringent dose control when administering probiotics alongside vaccines.

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