Pandemic preparedness: Addition of TLR agonists CpG+MPLA to emulsified H5 confers protection against H5N1 challenge after a single dose.

Abstract H5N1 vaccines adjuvanted in the oil-in-water emulsion MF59 are maintained Strategic National Stockpile for pre-pandemic preparedness. The US population currently naïve to H5 and a prime/boost regimen will likely be needed engender protective response. Ideally, rapid response pandemic influenza would benefit from being able induce protection single dose of vaccine. Here, we have used systems immunology approach mice examine effect formulating recombinant AddaVax alone or with CpG+MPLA. does not stimulate innate immune system, although oil droplets do act as nanocarrier antigen enhance B cell activation, presumably by BCR cross-linking. In vitro, germinal center reactions show inclusion CpG+MPLA (a combination adjuvant call IVAX-1) synergize maturation class-switching. Similarly, vivo, H5/IVAX-1 enhances both H5-specific T responses compared individual components. Single mRNA sequencing spleen cells after boost indicate H5/CpG+MPLA more similar each other but distinct H5/AddaVax H5/PBS. Unexpectedly, H5/AddaVax, all engendered 100% efficacy against lethal intranasal challenge virus, only dose. Our data potential certain adjuvants immunogenicity achieve vaccination. Supported AI160397. NIAID Grant AI160397