Virus-Like Particles for Antigen Delivery at Mucosal Surfaces

Abstract

Virus-like particles are a new type of vaccine platform that presents an attractive alternative to more traditional live-attenuated or inactivated/subunit vaccines. Virus-like particles (VLP) are composed of viral structural proteins that assemble spontaneously in cells, mimicking the live virus without the possibility of replication. They are readily recognized by the immune system, inducing both humoral and cellular immune responses. Here we review the development of VLP as vaccine delivery systems at mucosal surfaces. We first summarize the current status of VLP vaccines in general, and then discuss their use in mucosal vaccination approaches for several viruses that enter the host via the urogenital, respiratory or gastrointestinal tract.

Analysis of the humoral immune response against the envelope glycoprotein Gc of Schmallenberg virus reveals a domain located at the amino terminus targeted by mAbs with neutralizing activity

“…If the recently determined structure for BUNV virions (Bowden et al, 2013) holds true for SBV, the Gc Amino domain might be located at the tip of the Gc trimer. The most exposed surfaces of such a structural arrangement potently stimulate B-cells via interaction with receptors, resulting in immunogenic domains (reviewed by Schneider-Ohrum & Ross, 2012). Interestingly, a high frequency of mutations has been reported to occur in vitro and in vivo (Coupeau et al, 2013;Fischer et al, 2013) in the domain of Gc that includes SBV Gc Amino.…”

Enhanced Influenza Virus-Like Particle Vaccination with a Structurally Optimized RIG-I Agonist as Adjuvant

“…VLP are a versatile vaccine platform, capable of engaging the immune response by trafficking antigen into draining lymph nodes, stimulating antigen-presenting cells, and enhancing a robust adaptive immune response (7). The success of the versatile VLP vaccine platform is perhaps best illustrated with the human papillomavirus (HPV) vaccine which consists of HPV VLP as antigens, adjuvanted with alum (41).…”

“…Importantly, VLP can be genetically engineered to express vaccine antigens that represent a population of sequences and elicit cross-protective immune responses against multiple pathogens (10). Influenza VLP can be formed following coexpression of just three viral proteins-matrix (MA), hemagglutinin (HA), and neuraminidase (NA)-in a mammalian expression system; VLP express the major surface influenza proteins in the same conformation as found in the influenza virion and have been shown to stimulate a potent immune response (7).…”

“…Virus-like particles (VLP) are an attractive alternative to moretraditional live attenuated or split vaccines (7). VLP mimic the virus in structure and morphology but are noninfectious and thus possess a high safety profile that enhances their potential for future vaccine development against highly pathogenic strains (7).…”

A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

“…The antigen delivery vehicle also plays a major role, since inert subunit vaccines are poorly immunogenic compared to live vaccines when administered mucosally (2). New vaccinal approaches based on virus-like nanosized particles that could provide sufficient immunogenicity for mucosal vaccination have emerged lately (3). The self-assembly property of one or several viral proteins produced through recombinant technologies results in the formation of subviral particles ranging in size from about 20 to 100 nm (4).…”