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Abstract
Although annual vaccination reduces influenza-associated morbidity and mortality, surveillance mismatch and antigenic drift undermine the efficacy of seasonal flu vaccines. NIH initiatives to develop vaccine platforms that improve the breadth and longevity of vaccine-induced immune responses include more broadly reactive antigens including computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins. The consensus layering technique of COBRA methodology incorporates genomic sequences of influenza isolates to design subtype-specific rHA antigens more representative of wild-type HAs. We compare the efficacy of delivering COBRA rHA antigen in VacSIM, an alternative delivery platform utilizing the self-assembling (RADA)4 peptide, versus Addavax, a conventional oil-in-water emulsion, using prime-boost vaccination of C57BL/6 mice. Delivery of P1 COBRA rHA+CpG in VacSIM produced the highest endpoint titers and levels of protection against influenza challenge. Our results indicate the VacSIM hydrogel platform serves as a promising means to enhance the efficacy of novel influenza vaccine candidates, including COBRA rHA antigens.