Sustained Vaccine Exposure Elicits More Rapid, Consistent, and Broad Humoral Immune Responses to Multivalent Influenza Vaccines

Abstract With the ever‐present threat of pandemics, it is imperative vaccine technologies eliciting broad and durable immunity to high‐risk pathogens are developed. Yet, current annual influenza vaccines, for example, fail to provide robust immunity against the 3–4 homologous strains they contain, let alone heterologous strains. Herein, this study demonstrates that sustained delivery of multivalent influenza vaccines from an injectable polymer‐nanoparticle (PNP) hydrogel technology induces more rapid, consistent, and potent humoral immune responses against multiple homologous viruses, as well as potent responses against heterologous viruses and potential pandemic subtypes H5N1, H7N9 and H9N2. Further, admixing PNP hydrogels with commercial influenza vaccines results in stronger hemagglutination inhibition against both heterologous and homologous viruses. Additional investigation shows this enhanced potency and breadth arise from higher affinity antibodies targeting both the hemagglutinin stem and head. Overall, this simple and effective sustained delivery platform for multivalent annual influenza vaccines generates durable, potent, and remarkably broad immunity to influenza.