Influenza remains a threat to global public health, causing millions of infections and thousands of fatalities worldwide annually while lacking efficacious treatment modalities. Prophylactic vaccination is recommended as the most effective method to ameliorate influenza's burden on human health. The inactivated influenza vaccine (IIV), including three or four selected influenza strains, is the most commonly used influenza vaccine, demonstrating both safety and efficacy across diverse age cohorts. Nonetheless, the rapid evolution of influenza viruses leads to mismatches between vaccine strains and circulating variants, diminishing vaccine effectiveness. In response to the antigenic hypervariability in influenza viruses, the computationally optimized broadly reactive antigen (COBRA) technology was developed and has been updated based on recently emerged strains. This approach uses multiple layered consensus building to design hemagglutinin (HA) or neuraminidase (NA) constructs capable of eliciting cross-reactive antibodies. Considering the long history of IIV in human use, this study investigated the effectiveness of whole inactivated vaccine (WIV) and split inactivated vaccine (SIV) expressing COBRA HA proteins, aiming to design a promising candidate for the next-generation influenza vaccine. To comprehensively evaluate the efficacy of COBRA-IIVs, this study employed diverse animal models, encompassing both naïve and pre-immune states, alongside varied challenge scenarios. The findings proved that COBRA-IIVs effectively induced broadly reactive antibodies following two vaccinations, with heightened breadth observed in pre-immune models. Notably, antibody titers persist over 20 weeks post-vaccination, with sustained protection against viral challenge. The addition of the adjuvant AddaVax significantly enhanced vaccine efficacy, particularly for COBRA-SIV formulations. Furthermore, a single dose of COBRA-IIVs elicited robust and enduring antibody responses in pre-immune ferrets, with further enhancement conferred by adjuvanted administration. Notably, the novel adjuvant R-DOTAP surpassed AddaVax in augmenting both humoral and cellular immune responses, positioning it as a potential adjuvant for universal influenza vaccine (UIV) development. In ferret models, COBRA-IIV vaccination reduced viral infection and transmission and delayed viral shedding which could limit the virus spreading. Conclusively, these results underscore the promise of COBRA-IIV as a UIV candidate, providing supportive data for progression to clinical evaluation.