Abstract Introduction The selection of the right IBD control strategy is primarily based on the choice of the appropriate vaccine strain. High maternal IBD-specific antibodies (Abs) compete with the efficacy IBD vaccine, which necessitates the application of intermediate-plus vaccine strain. Methods A comparative experimental study was designed for evaluation of four different commercially available intermediateplus IBD vaccines in commercial broilers before complete weaning of IBD-specific maternal Abs. Results As determined by IBD- specific quantitative real-time polymerase chain reaction, three tested vaccine strains (228E, Winterfield H2512, and Winterfield 2512) were able to establish in the bursal tissues as early as six hours (hrs) post-vaccination (PV). Both the 228E and the Winterfield H2512 strains vaccinated groups had the highest viral load and replication rate in the bursal tissues at 24, 36, 48 and 72 hrs PV. Earlier seroconversion, 7-14 days PV, was observed in the case of Winterfield H2512, 228E, and Winterfield 2512 vaccinated birds compared to the Lukert vaccinated birds. The 228E strain was more virulent and induces the highest lesion score with severe degrees of lymphocyte depletion and necrosis which persisted up to 28 days PV. Conclusion Overall, the different intermediate-plus IBD strains possess variable early kinetics in the bursal tissues and eliciting antibody (Ab) responses differently withdifferent degrees of bursal lesions. The assessment of the intrabursal vaccine load together with humoral immunity and bursal damage lesion score are fundamental parameters in the evaluation of the intermediate-plus IBD vaccines.