Influenza viruses cause seasonal epidemics and represent a pandemic risk. With current vaccine methods struggling to protect populations against emerging strains, there is a demand for a next-generation flu vaccine capable of providing broad protection. Recombinant biotechnology, combined with nanomedicine techniques, could address this demand by increasing immunogenicity and directing immune responses toward conserved antigenic targets on the virus. Various nanoparticle candidates have been tested for use in vaccines, including virus-like particles, protein and carbohydrate nanoconstructs, antigen-carrying lipid particles, and synthetic and inorganic particles modified for antigen presentation. These methods have yielded some promising results, including protection in animal models against antigenically distinct influenza strains, production of antibodies with broad reactivity, and activation of potent T cell responses. Based on the evidence of current research, it is feasible that the next generation of influenza vaccines will combine recombinant antigens with nanoparticle carriers.
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.
Malaria is transmitted by protozoan parasites of the Plasmodium genus, via mosquito vectors. Highly effective vaccines could be a valuable tool to control the disease, but have remained elusive, in part due to the complex lifecycle of the parasite. Transmission‐blocking vaccines (TBVs) take the unconventional approach of targeting the mosquito stages of the parasite life cycle. TBVs are yet to be tested in large‐scale human trials, but represent a prominent area of interest for malaria vaccine research and development. Because TBVs rely on passive antibody transfer from a blood meal to the mosquito midgut, techniques to boost host antibody generation are a focus of investigation. In this review, immunostimulants and delivery systems for conjugating, self‐assembling, or coadministrating TBV antigens and adjuvants are summarized.
A method is developed for membrane labeling of erythrocytes with porphyrin‐phospholipid (PoP). To generate a concentrated PoP solution for labeling human red blood cells (RBCs), various surfactants and solvents are screened to identify conditions that avoid hemolysis while minimizing nonspecific PoP coprecipitation with RBCs in the pellet during centrifugation washes. Cholate, Tween 80, and Tween 40 are identified as useful surfactants for this purpose. When labeled RBCs are mixed with unlabeled ones, substantial nonspecific PoP exchange is observed. Egg‐yolk lecithin is included in a washing buffer to remove loosely bound PoP and reduce PoP exchange with unlabeled erythrocytes, based on flow cytometry and photodynamic hemolysis assays. Murine RBCs that are labeled with 64Cu‐chelated PoP display altered biodistribution with longer blood circulation relative to directly administered 64Cu‐chelated PoP.
A self-assembling influenza virus vaccine platform that seamlessly converts soluble antigens into nanoparticles is demonstrated with various H1N1 and H3N2 influenza antigens to protect mice against influenza virus challenge following intranasal vaccination. Mucosal immune responses following liposome delivery to lung antigen-presenting cells are demonstrated.
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