Transcutaneous vaccination with virus-like particles

Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Vaccine (Impact Factor: 3.62). 07/2006; 24(26):5406-12. DOI: 10.1016/j.vaccine.2006.03.052
Source: PubMed


Virus-like particles (VLP) are inert, empty capsids of viruses, which contain no DNA/RNA from the virus itself. However they retain the structure of a virus and they can be engineered to have antigens attached. We have constructed VLP, derived from Rabbit hemorrhagic disease virus, and shown they are highly immunogenic. We tested the capacity of these engineered VLP to induce immune responses when they are administered to mice via the transcutaneous route. This route of vaccination is important, in order to generate mucosal protection. Our data showed that VLP are taken up by dendritic cells (DC), antigen-presenting cells that are essential to initiate acquired immune responses. The VLP induced an increase in expression of CD40, CD80 and CD86 but required an adjuvant, CpG DNA oligo-deoxy nucleotides (ODN) motifs, to enhance these responses. In vivo testing has also shown that the VLP, when wiped on to the skin in conjunction with immunostimulatory CpG, induce Ag-specific immune responses, typified by high levels of IFN-gamma and IgG1.

Download full-text


Available from: Margaret A Baird
  • Source
    • "VLP assembly was confirmed by electron microscopy. This synthesis and processing of RHDV VLP leads to consistent production of purified particles ∼40 nm in diameter, which have been shown to be effective antigen delivery platforms [4], [6], [10], [33]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Internalization of peptides by antigen presenting cells is crucial for the initiation of the adaptive immune response. Mannosylation has been demonstrated to enhance antigen uptake through mannose receptors, leading to improved immune responses. In this study we test the effect of surface mannosylation of protein-based virus-like particles (VLP) derived from Rabbit hemorrhagic disease virus (RHDV) on uptake by murine and human antigen presenting cells. A monomannoside and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP capsid protein, providing approximately 270 mannose groups on the surface of each virus particle. VLP conjugated to the mannoside or dimannoside exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages and B cells as well as human dendritic cells and macrophages. This uptake was inhibited by the inclusion of mannan as a specific inhibitor of mannose specific uptake, demonstrating that mannosylation of VLP targets mannose receptor-based uptake. Consistent with mannose receptor-based uptake, partial retargeting of the intracellular processing of RHDV VLP was observed, confirming that mannosylation of VLP provides both enhanced uptake and modified processing of associated antigens.
    Full-text · Article · Aug 2014 · PLoS ONE
  • Source
    • "It is considered that VLPs are taken up and cross-presented to T cells by professional antigen presenting cells (APCs) such as dendritic cells (DCs) (Win et al., 2011). Although several VLPs were reported to require the co-administration of adjuvants (Qian et al., 2006; Storni et al., 2004; Young et al., 2006) for the induction of CTLs, many kinds of VLPs could induce potent cell-mediated immune responses even without adjuvants (Buonaguro et al., 2002; Lacasse et al., 2008). However, the adjuvant-like role of viral structural proteins is poorly understood. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A(⁎)02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A(⁎)02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties.
    Full-text · Article · Jan 2014 · Virology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract: Human noroviruses (HuNoV) are the leading cause of food- and water-borne non-bacterial gastroenteritis worldwide. In this study we delineated the local and systemic immune responses to a GII. HuNoV (HS66 strain) in gnotobiotic pigs and calves and evaluated the immune responses to HuNoV-HS66 virus-like particles vaccines adjuvanted with either ISCOM or mLT and also protection against the homologous virus in Gn pigs. In our study, low antibody titers and antibody-secreting cell (ASC) numbers were elicited in the HuNoV-HS66-inculated pigs, but 65% of the pigs seroconverted. A higher Th1 (high IL-12 but low and transient IFN-gamma), but also low Th2 (IL-4 and IL-10), low transient pro-inflammatory (IL-6) cytokine and delayed innate (IFN-alpha) responses were induced by the HuNoV-HS66 in the serum of the Gn pigs. Intestinal IFN-alpha and IL-12 (late) were also significantly elevated after infection. Higher numbers of Th1 (IL-12 and IFN-gamma) cytokine-secreting cells (CSC) were elicited when compared to Th2 (IL-4) and pro-inflammatory (IL-6) cytokines. The HuNoV-HS66 caused diarrhea and intestinal lesions, mainly in the proximal part of the intestine of one of the calves euthanized at PID 3. Viral shedding was detected from post-inoculation day 1-6 and 67% of the animals seroconverted with HuNoV-HS66-specific IgA and IgG antibodies. Both Th1 (IL-12 and IFN-gamma) and Th2/T-reg (IL-10) cytokines, but also pro-inflammatory (TNF-alpha) were induced in the serum and fecal samples of the HuNoV-HS66-inoculated calves. One-hundred percent seroconversion rate was observed in the vaccinated pigs, regardless of the vaccine regimen, and 100% of coproconversion was detected in the VLP+ISCOM pigs compared to 75% of the VLP+mLT group. However, only 57% of the control pigs shed virus post-challenge. The VLP+mLT vaccine induced a balanced Th1/Th2 response, whereas the VLP+ISCOM induced a more Th2 biased response, but both vaccine regimens induced high levels of protection against virus shedding and diarrhea. 2.24 MB Title from first page of PDF file. Thesis (Ph. D.)--Ohio State University, 2007. Includes bibliographical references (p. 281-328). Available online via OhioLINK's ETD Center System requirements: World Wide Web browser and PDF viewer.
    Preview · Article ·
Show more