Biomimetic Antigenic Nanoparticles Elicit Controlled Protective Immune Response to Influenza

Abstract

Here we present a biomimetic strategy towards nanoparticle design for controlled immune response through encapsulation of conserved internal influenza proteins on the interior of virus like particles (VLPs) to direct CD8+ cytotoxic T cell protection. Programmed encapsulation and sequestration of the conserved nucleoprotein (NP) from influenza on the interior of a VLP, derived from the bacteriophage P22, results in a vaccine that provides multi-strain protection against 100 times lethal doses of influenza in an NP specific CD8+ T cell-dependent manner. VLP assembly and encapsulation of the immunogenic NP cargo protein is the result of a genetically programmed self-assembly making this strategy amendable to the quick production of vaccines to rapidly emerging pathogens. Addition of adjuvants or targeting molecules were not required for eliciting the protective response.

Structural Basis for the Development of Avian Virus Capsids That Display Influenza Virus Proteins and Induce Protective Immunity

“…Whereas attenuation of virulence and chemical inactivation are the oldest (and still-used) approaches to classical vaccine production, new strategies for human and veterinary medicine are constantly emerging due to improvements in safety and efficiency, among other factors (41). Approaches that use recombinant viral vector-and subunit (VLP)-based vaccines have been demonstrated to offer effective protection against diseases (42)(43)(44)(45). Our model for vaccine development is the IBDV VP2 capsid protein, which we tested as a platform to anchor foreign antigens.…”

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

“…The larger nanobubbles were prepared using two distinct morphologies of a viruslike particle (VLP) derived from the Salmonella typhimurium bacteriophage P22 capsid. This VLP is a protein cage composed of 420 subunits of a 46.6 kDa coat protein that assemble into an icosahedral capsid with the aid of a scaffolding protein [8][9][10][11]. The first VLP morphology used here is the empty shell formulation of the VLP (P22 ES), in which the scaffolding protein has been removed; the resulting protein cage has an outer diameter of approximately 58 nm and an inner diameter of approximately 48 nm.…”

“…To this end, we present the development of a novel protein-based nanoparticle contrast agent comprised of nano-sized protein cage architectures that are filled with perfluoropropane (C 3 F 8 ) gas. The protein assemblies used to make these "nanobubble" contrast agents are apoferritin (approximately 12 nm outer diameter) [7] and a virus-like particle (VLP) derived from the Salmonella typhimurium bacteriophage P22 capsid (approximately 60 nm outer diameter) [8][9][10][11].…”

“…Protein cage structures such as those mentioned above have been studied for their potential in materials synthesis [7,12], catalysis [13,14], drug and gene delivery [15,16], bio-imaging [17][18][19], cell targeting [20,21], and vaccine development [11]. VLPs in particular are promising, as they exist in a large range of sizes (tens to hundreds of nanometers), have well-defined, monodisperse structures, can be purified in large quantities, and can be easily modified both genetically and chemically [22][23][24][25][26][27].…”

Fabrication of nanoadjuvant with poly-e-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity

“…19 The past decade has seen important developments in the use of nanotechnology in the field of vaccine adjuvants and carrier vehicles, especially polymeric materials in the nano-and microranges. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] These studies hold great promise to elicit complex immune responses from all branches of immunity for effective and safe vaccination against major infections that have escaped effective vaccination.…”