Background The velogenic-Newcastle Disease Virus (v-NDV) causes an important disease in chicken, associated with serious economic losses to the global poultry industry. This research evaluated the immunity in broilers administered a developed bivalent vaccine, aiming at protection against predominant Middle Eastern strains of genotypes VI and VII of v-NDV. The completely randomized design implemented in this evaluation included eight treatments, differing in birds being administered or deprived of the developed vaccine, with a difference in type of challenge, either by v-NDV strain(s) of genotype VI, VII, or both. Vaccination was administered subcutaneously at 6 and 21 d of age, followed by an intra-pectoral challenge at the age of 28 d. Results The acquired humoral immunity by vaccinated and challenged birds to Hemagglutinin (H) protein was the highest at market age of 40 d, compared to challenged birds deprived of vaccination, and to vaccinates deprived of challenge (P<0.05). The same statistical difference pattern was obtained by the cell-mediated immunity (CMI), represented by birds’ level of serum IFN- γ . The type of challenge by either strain(s) of genotype VI, VII, or VI+VII did affect statistically the cross reactivity of acquired humoral immunity specific to H protein of homologous versus heterologous strains. The absence of humoral immunity and the low IFN- γ levels at 28 d of age in challenged birds deprived of vaccination lead to highest mortality, and lowest performance compared to vaccinates and challenged, vaccinates and deprived of challenge, and unvaccinated-unchallenged birds (P<0.05). Conclusions The developed bivalent vaccine was able to induce enough humoral and CMI responses, enabling protection of the broilers against production losses by each of the three types of v-NDV challenges. It is recommended to conduct future studies to evaluate such types of vaccines in chicken breeders and commercial layers, reared in various world’s zones with existing endemicity of v-NDV.