Toward a universal influenza virus vaccine: prospects and challenges

Current influenza virus vaccines are annually reformulated to elicit protection by generating an immune response toward the virus strains that are predicted to circulate in the upcoming influenza season. These vaccines provide limited protection in cases of antigenic mismatch, when the vaccine and the circulating viral strains differ. The emergence of unexpected pandemic viruses presents an additional challenge to vaccine production. To increase influenza virus preparedness, much work has been dedicated to the development of a universal vaccine. Focusing on regions of viral proteins that are highly conserved across virus subtypes, vaccine strategies involving the matrix 2 protein, stalk domain of the hemagglutinin, and multivalent approaches have provided broad-based protection in animal models and show much promise. This review summarizes the most encouraging advances in the field with a focus on novel vaccine designs that have yielded promising preclinical and clinical data.