A liposome-displayed hemagglutinin vaccine platform protects mice and ferrets from heterologous influenza virus challenge.

Recombinant influenza virus vaccines based on hemagglutinin (HA) hold the potential to accelerate production timelines and improve efficacy relative to traditional egg-based platforms. Here, we assess a vaccine adjuvant system comprised of immunogenic liposomes that spontaneously convert soluble antigens into a particle format, displayed on the bilayer surface. When trimeric H3 HA was presented on liposomes, antigen delivery to macrophages was improved in vitro, and strong functional antibody responses were induced following intramuscular immunization of mice. Protection was conferred against challenge with a heterologous strain of H3N2 virus, and naive mice were also protected following passive serum transfer. When admixed with the particle-forming liposomes, immunization reduced viral infection severity at vaccine doses as low as 2 ng HA, highlighting dose-sparing potential. In ferrets, immunization induced neutralizing antibodies that reduced the upper respiratory viral load upon challenge with a more modern, heterologous H3N2 viral strain. To demonstrate the flexibility and modular nature of the liposome system, 10 recombinant surface antigens representing distinct influenza virus strains were bound simultaneously to generate a highly multivalent protein particle that with 5 ng individual antigen dosing induced antibodies in mice that specifically recognized the constituent immunogens and conferred protection against heterologous H5N1 influenza virus challenge. Taken together, these results show that stable presentation of recombinant HA on immunogenic liposome surfaces in an arrayed fashion enhances functional immune responses and warrants further attention for the development of broadly protective influenza virus vaccines.

Pullulan dialdehyde crosslinked gelatin hydrogels with high strength for biomedical applications.

Herein the construction of a strong gelatin hydrogel is presented by using pullulan dialdehyde (PDA) as a macromolecular crosslinker. The resultant PDA crosslinked gelatin hydrogels (G-PDA) exhibit extremely high mechanical strength, manifested in the achieved optimal compressive stress of 5.80 MPa at 80% strain, which is up to 152 times higher than pure gelatin hydrogel. The G-PDA were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The extent of crosslinking was determined by ninhydrin assay. The results suggested that the synergistic effect of dual-crosslinking, which is composed of short- and long-range covalent crosslinking and thermoreversible physical crosslinking, may played a key role in enhancing the load-bearing capacity of ensuing hydrogels. The swelling and enzymatic degradation of G-PDA are gradually limited with increasing PDA concentration. The result from MTT assay demonstrated that G-PDA is non-cytotoxic against MC3T3 cells, regardless of the concentrations of PDA.

Thermal Stabilization of Viral Vaccines in Low-Cost Sugar Films.

Most currently available vaccines, particularly live vaccines, require the cold chain, as vaccine efficacy can be significantly hampered if they are not stored in a temperature range of 2-8 °C at all times. This necessity places a tremendous financial and logistical burden on vaccination programs, particularly in the developing world. The development of thermally stable vaccines can greatly alleviate this problem and, in turn, increase vaccine accessibility worldwide. In this paper, we detail a simple and cost-effective method for stabilizing live vaccines that uses FDA-approved materials. To this end, we dried enveloped DNA (Herpes Simplex Virus type 2) and RNA (Influenza A virus) viral vaccines in a pullulan and trehalose mixture. The results of these studies showed that the live-attenuated HSV-2 vaccine retained its efficacy for at least 2 months of storage at 40 °C, while the inactivated influenza vaccine was able to retain its immunogenicity for at least 3 months of storage at 40 °C. This work presents a simple approach that allows thermo-sensitive vaccines to be converted into thermo-stable vaccines that do not require refrigeration, thus contributing to the improvement of vaccine deployment throughout the world.