We have designed a membrane-anchored form of the Toll-like receptor 5 ligand flagellin, the major proinflammatory determinant of enteropathogenic Salmonella, which was found to be glycosylated and expressed on cell surfaces. A chimeric influenza virus-like particle (

This study demonstrates that VLP vaccination provides effective protection against RSV infection. VLPs containing RSV-F and/or RSV-G are potential vaccine candidates against RSV.

Development of an influenza vaccine that provides broadly cross-protective immunity has been a scientific challenge for more than half a century. This study presents an approach to overcome strain-specific protection by supplementing conventional vaccines with virus-like particles (VLPs) containing the conserved M2 protein (M2 VLPs) in the absence of adjuvants. We demonstrate that an inactivated influenza vaccine supplemented with M2 VLPs prevents disease symptoms without showing weight loss and confers complete cross protection against lethal challenge with heterologous influenza A viruses including the 2009 H1N1 pandemic virus as well as heterosubtypic H3N2 and H5N1 influenza viruses. Cross-protective immunity was long-lived, for more than 7 mo. Immune sera from mice immunized with M2 VLP supplemented vaccine transferred cross protection to naive mice. Dendritic and macrophage cells were found to be important for this cross protection mediated by immune sera. The results provide evidence that supplementation of seasonal influenza vaccines with M2 VLPs is a promising approach for overcoming the limitation of strain-specific protection by current vaccines and developing a universal influenza A vaccine.

New light-activated antimicrobial materials with a potentially wide range of possible uses in civilian settings were synthesized by the grafting of protoporphyrin IX and zinc protoporphyrin IX to nylon fibers. These fibers were shown to be active against Staphylococcus aureus at light exposures of 10,000 lux and greater and against Escherichia coli at 60,000 lux. They were ineffective against both strains in the absence of light. At 40,000 lux, these fibers showed increased antimicrobial activity against S. aureus with increasing exposure time.

Previously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.

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The quality of immune responses induced by DNA vaccination depends on the site of DNA administration, the expression, and the properties of the encoded antigen. In the present study, we demonstrate that intravenous hydrodynamic HIV-1 envelope DNA injection resulted in high levels of expression of HIV-1 envelope antigen in the liver. When compared to the administration of DNA by i.n., i.d., i.m., and i.splenic routes, hydrodynamic vaccination induced, upon DNA boosting, levels of HIV-1 envelope-specific antibodies 40-fold higher than those elicited by the other routes tested. Hydrodynamic vaccination with 1 microg DNA induced higher humoral responses than 100 microg DNA given intramuscularly in the prime-boost regimen. High levels of envelope-specific IgG and IgA antibodies were induced in genital tract secretions after two doses of DNA followed by intranasal boosting with recombinant HIV-1 gp120 protein. Furthermore, two doses of 100 microg DNA generated interferon-gamma production in approximately 4.3+/-1.7% of CD8(+) splenocytes after in vitro stimulation with HIV-1 envelope peptides. These results demonstrate that DNA vaccines targeted to tissues with high proteosynthetic activity, such as the liver, results in enhanced immune responses.

No abstract