The genetic, biophysical and immunological studies of a self-adjuvanted protein nanoparticle

Adjuvant is required for boosting the immune responses for subunit vaccine. An emerging category of vaccine adjuvant is the self-assembling peptide that forms fibril and stimulates both humoral and cellular immunities. Based on our previous finding that a stabilized self-assembled protein nanoparticle (PNP), also called Vaccine Delivery system X (VADEX), assembled from a fusion protein composed of an amphipathic helical peptide and a superfolder green fluorescent protein can stimulate long lasting immune responses to an inserted peptide. In this report, we further introduced split-GFP technology into VADEX and evaluated the role of the amphipathic helical peptide integrity, thermal stability of PNP and the effect of self-adjuvant in antibody affinity maturation of this new platform, VADEX-pro. Our result shows the significance of amphipathic helical peptide sequence integrity in PNP assembly and the thermal stability. The immunological results provide the first evidence that the VADEX-pro PNP possess a self-adjuvant activity that is superior to a clinical stage adjuvant when evaluating the antibody binding affinity. Application of VADEX-pro based protein nanoparticle in vaccine and therapeutic antibody development will likely improve the quality of humoral immune responses.