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Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. [ABSTRACT FROM AUTHOR]

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Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in adapting to new virus variants, reliance on cold chain supply networks, and administration by hypodermic injection. Microneedle (MN) patches, which are made of an array of micron-scale, solid needles that painlessly penetrate into the upper layers of the skin and dissolve to deliver vaccines intradermally, simplify vaccination and can thereby increase vaccine access, especially in resource-constrained or emergency settings. The present study describes a novel MN technology, which combines EBOV glycoprotein (GP) antigen with a polyphosphazene-based immunoadjuvant and vaccine delivery system (poly[di(carboxylatophenoxy)phosphazene], PCPP). The protein-stabilizing effect of PCPP in the microfabrication process enabled preparation of a dissolvable EBOV GP MN patch vaccine with superior antigenicity compared to a non-polyphosphazene polymer-based analog. Intradermal immunization of mice with polyphosphazene-based MN patches induced strong, long-lasting antibody responses against EBOV GP, which was comparable to intramuscular injection. Moreover, mice vaccinated with the MN patches were completely protected against a lethal challenge using mouse-adapted EBOV and had no histologic lesions associated with ebolavirus disease. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a global disease burden, and a preventive vaccine is needed to control or eradicate the virus. Despite the advent of effective antiviral therapy, this treatment is not accessible to many patients and does not prevent reinfection, making chronic hepatitis C an ongoing global health problem. Thus, development of a prophylactic vaccine will represent a significant step toward global eradication of HCV. HCV exhibits high genetic variability, which leads frequently to immune escape. However, a considerable challenge faced in HCV vaccine development is designing an antigen that elicits broadly neutralizing antibodies. Here, we characterized the immunogenicity of a vaccine based on a soluble, secreted form of the E1E2 envelope heterodimer (sE1E2.LZ). Sera from mice immunized with sE1E2.LZ exhibited an anti-E1E2-specific response comparable to mice immunized with membrane-bound E1E2 (mbE1E2) or a soluble E2 ectodomain (sE2). In competition-inhibition ELISA using antigenic domain-specific neutralizing and nonneutralizing antibodies, sera from sE1E2.LZ-immunized mice showed nearly identical or stronger competition toward neutralizing antibodies when compared with mbE1E2. In contrast, sera from mice immunized with sE2, and to a lesser extent mbE1E2, competed more effectively with nonneutralizing antibodies. An assessment of neutralization activity using both HCV pseudoparticles and cell culture-derived infectious HCV showed that immunization with sE1E2.LZ elicited the broadest neutralization activity of the three antigens, and sE1E2.LZ induced neutralization activity against all genotypes. These results indicate that our native-like soluble glycoprotein design, sE1E2.LZ, induces broadly neutralizing antibodies and serves as a promising vaccine candidate for further development. [ABSTRACT FROM AUTHOR]