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Infectious bursal disease has hampered the development of commercial poultry production in Ghana, with outbreaks continually occurring despite the introduction of the harmonized national poultry vaccination protocol (HNPVP) that incorporates two types of live IBD vaccines. One major reported reason for these vaccination failures is the vaccine neutralization by maternally-derived antibodies (MDA). This study compared the antibody titres of layers vaccinated with the HNPVP to layers vaccinated with VAXXITEK HVT+IBD, a viral vectored vaccine. An agar gel immunodiffusion test and an indirect enzyme linked immunosorbent assay (ELISA) were used to detect and quantify antibodies. The results of this experiment show that high MDA did not affect VAXXITEK HVT + IBD as there was a measurable antibody response with high titre values. However, the delay before this antibody response and the resultant low antibody levels at the most susceptible period may create an opportunity for field infection. However high MDA interfere with and can neutralize live IBD vaccines even when they are applied strictly as advised in the HNPVP. It is therefore quite likely that a significant portion of the reported IBD vaccination failures in Ghana are due to failure of the HNPVP due to interference with MDA hence specific ‘farm-tailored’ vaccination schedules based on flock profiling, and recombinant vectored vaccines that have been shown to produce universal protection unaffected by high MDA may be the solutions to post vaccination outbreak commonly observed in Ghana.