BECC Adjuvanted Vaccine Provides Broad Protection from Homologous and Heterologous Influenza A Virus Infections
AdvisorFrieman, Matthew B.
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AbstractInfluenza A virus (IAV) is a leading cause of mild to severe respiratory disease worldwide with significant infections resulting in hospitalization or death, especially in older individuals, young children, and people with comorbidities. Because the influenza virus has a high rate of mutation, this allows the virus to evade the host immune system against new variants, new vaccines are produced annually to match circulating strains. FluAd, is currently the only approved influenza vaccine formulated with the adjuvant MF59, a squalene oil emulsion, to create a stronger immune response to the vaccination and is limited for use in people 65 years and older. Classic adjuvants such as oil emulsions and alum are not universally effective and potentiate toward a T helper 2 (Th2) response (effective versus extracellular pathogens), while another often-used vaccine adjuvant, monophosphoryl lipid A, skews toward a Th1 response (effective versus intracellular pathogens). Unique adjuvants have been created using the Bacterial Enzymatic Combinatorial Chemistry (BECC) system to produce novel Toll like receptor 4 (TLR4) immunostimulatory molecules. These molecules drive a balanced Th1/Th2 response and enhanced immunogenicity in the context of an influenza virus vaccine candidate as well as other vaccine platforms. These BECC adjuvanted vaccines display superior protection to challenge from a homologous IAV strain in a BALB/c mouse model, even in aged mice with a single prime vaccination. More important, these vaccines stimulate the production of broadly reactive antibody to the hemagglutinin stem and protection against heterologous IAV strain infection, possibly skirting the need to formulate new influenza vaccine annually.
DescriptionMolecular Microbiology and Immunology
University of Maryland, Baltimore