A thermally stable protein nanoparticle that stimulates long lasting humoral immune response

Abstract

AbstractThermally stable vaccine platform is considered to be the missing piece of vaccine technology. In this article, we are reporting the development of a novel protein nanoparticle and evaluating its ability in withstanding extended high temperature incubation and stimulating long lasting humoral immune response. This protein nanoparticle is assembled from a fusion protein composed of an amphipathic helical peptide derived from M2 protein of H5N1 influenza virus (AH3) and a super folder green fluorescent protein(sfGFP). The proposed structure of this protein nanoparticle is modeled according to transmission electronic microscope (TEM) images of protein nanoparticle. From this proposed protein model, we have generated a mutant with two gain-of-function mutations that function synergistically on particle stability. Protein nanoparticle assembled from this gain-of-function mutant is able to remove a hydrophobic patch from the surface of protein nanoparticle. This gain-of-function mutant also contributes to higher thermostability of protein nanoparticle and stimulates long lasting humoral immune response after single immunization. This protein nanoparticle shows increasing particle stability in higher temperature and higher salt concentration. This novel protein nanoparticle may serve as a thermal-stable platform for vaccine development.