Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity

Lassa mammarenavirus (LASV) is a rodent-borne arenavirus endemic to several West African countries. It is the causative agent of human Lassa fever, an acute viral hemorrhagic fever disease. To date, no therapeutics or vaccines against LASV have obtained regulatory approval. Polyclonal neutralizing antibodies derived from hyperimmunized animals may offer a useful strategy for prophylactic and therapeutic intervention to combat human LASV infections. The LASV envelope surface glycoprotein complex (GP) is the major target for neutralizing antibodies, and it is the main viral antigen used for the design of an LASV vaccine. Here, we assessed the immunogenic potential of mammalian cell-derived virus-like particles (VLPs) expressing GP from the prototypic LASV strain Josiah in a native-like conformation as the sole viral antigen. We demonstrate that an adjuvanted prime-boost immunization regimen with GP-derived VLPs elicited neutralizing antibody responses in rabbits, suggesting that effective antigenic epitopes of GP were displayed. Notably, these antibodies exhibited broad reactivity across five genetic lineages of LASV. VLP-based immunization strategies may represent a powerful approach for generating polyclonal sera containing cross-reactive neutralizing antibodies against LASV

Characterization of the Human Cytomegalovirus Protein pUL71 and its Impact on viral Morphogenesis in Fibroblasts, Endothelial Cells and Macrophages

We could show that HCMV morphogenesis is comparable in fibroblasts, endothelial cells and macrophages and that the absence or the functional impairment of the HCMV tegument protein pUL71 is affecting viral morphogenesis in all investigated cell types in a similar manner. pUL71 is associated with membranes within the AC at late stages of infection, and its absence causes impairment of secondary envelopment, morphological alterations of vesicles within the AC, and influences MVBs in infected fibroblasts, HUVEC, and MDM. Particularly a pUL71 palmitoylation site and a leucine zipper like motif are of great importance for pUL71 function and HCMV morphogenesis, while a C-terminal tetra-lysine motif only augments secondary envelopment. In contrast, a Vps4 interacting motif of pUL71seems to be not important for HCMV morphogenesis

Peptide Amphiphile Micelle Vaccine Size and Charge Influence the Host Antibody Response

Vaccines are one of the best health care advances ever developed, having led to the eradication of smallpox and near eradication of polio and diphtheria. While tremendously successful, traditional vaccines (i.e., whole-killed or live-attenuated) have been associated with some undesirable side effects, including everything from mild injection site inflammation to the autoimmune disease Guillain–Barré syndrome. This has led recent research to focus on developing subunit vaccines (i.e., protein, peptide, or DNA vaccines) since they are inherently safer because they deliver only the bioactive components necessary (i.e., antigens) to produce a protective immune response against the pathogen of interest. However, a major challenge in developing subunit vaccines is overcoming numerous biological barriers to effectively deliver the antigen to the secondary lymphoid organs where adaptive immune responses are orchestrated. Peptide amphiphile micelles are a class of biomaterials that have been shown to possess potent self-adjuvanting vaccine properties, but their optimization capacity and underlying immunostimulatory mechanism are not well understood. The present work investigated the influence of micelle size and charge on the materials’ bioactivity, including lymph node accumulation, cell uptake ability, and immunogenicity. The results generated provide considerable insight into how micelles exert their biological effects, yielding a micellar toolbox that can be exploited to either enhance or diminish host immune responses. This exciting development makes peptide amphiphile micelles an attractive candidate for both immune activation and suppression applications