Most cited article - PubMed ID 22006508
Complexes of streptavidin-fused antigens with biotinylated antibodies targeting receptors on dendritic cell surface: a novel tool for induction of specific T-cell immune responses
Systems of antigen delivery into antigen-presenting cells represent an important novel strategy in chicken vaccine development. In this study, we verified the ability of Rous sarcoma virus (RSV) antigens fused with streptavidin to be targeted by specific biotinylated monoclonal antibody (anti-CD205) into dendritic cells and induce virus-specific protective immunity. The method was tested in four congenic lines of chickens that are either resistant or susceptible to the progressive growth of RSV-induced tumors. Our analyses confirmed that the biot-anti-CD205-SA-FITC complex was internalized by chicken splenocytes. In the cytokine expression profile, several significant differences were evident between RSV-challenged progressor and regressor chicken lines. A significant up-regulation of IL-2, IL-12, IL-15, and IL-18 expression was detected in immunized chickens of both regressor and progressor groups. Of these cytokines, IL-2 and IL-12 were most up-regulated 14 days post-challenge (dpc), while IL-15 and IL-18 were most up-regulated at 28 dpc. On the contrary, IL-10 expression was significantly down-regulated in all immunized groups of progressor chickens at 14 dpc. We detected significant up-regulation of IL-17 in the group of immunized progressors. LITAF down-regulation with iNOS up-regulation was especially observed in the progressor group of immunized chickens that developed large tumors. Based on the increased expression of cytokines specific for activated dendritic cells, we conclude that our system is able to induce partial stimulation of specific cell types involved in cell-mediated immunity.
- MeSH
- Antigens, Viral immunology MeSH
- Immunity, Cellular immunology MeSH
- Antigens, CD immunology MeSH
- Cytokines physiology MeSH
- Dendritic Cells immunology virology MeSH
- Chickens immunology virology MeSH
- Lectins, C-Type immunology MeSH
- Antibodies, Bispecific immunology MeSH
- Sarcoma, Avian immunology prevention & control MeSH
- Receptors, Cell Surface immunology MeSH
- Minor Histocompatibility Antigens immunology MeSH
- Viral Vaccines immunology MeSH
- Rous sarcoma virus immunology MeSH
- Animals, Congenic immunology virology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antigens, Viral MeSH
- Antigens, CD MeSH
- Cytokines MeSH
- DEC-205 receptor MeSH Browser
- Lectins, C-Type MeSH
- Antibodies, Bispecific MeSH
- Receptors, Cell Surface MeSH
- Minor Histocompatibility Antigens MeSH
- Viral Vaccines MeSH
The development of influenza A virus (IAV) vaccines, which elicits cross-strain immunity against seasonal and pandemic viruses is a major public health goal. As pigs are susceptible to human, avian, and swine-adapted IAV, they would be key targets of so called universal IAV vaccines, for reducing both the zoonotic risk and the economic burden in the swine industry. They also are relevant preclinical models. However, vaccination with conserved IAV antigens (AGs) in pigs was reported to elicit disease exacerbation. In this study, we assessed whether delivery strategies, i.e., dendritic cell (DC) targeting by the intradermal (ID) or intramuscular (IM) routes, impact on the outcome of the vaccination with three conserved IAV AGs (M2e, NP, and HA2) in pigs. The AGs were addressed to CD11c by non-covalent binding to biotinylated anti-CD11c monoclonal antibody. The CD11c-targeted AGs given by the ID route exacerbated disease. Conversely, CD11c-targeted NP injected by the IM route promoted T cell response compared to non-targeted NP. Furthermore, the conserved IAV AGs injected by the IM route, independently of DC targeting, induced both a reduction of viral shedding and a broader IgG response as compared to the ID route. Our findings highlight in a relevant animal species that the route of vaccine delivery impacts on the protection induced by conserved IAV AGs and on vaccine adverse effects. Finally, our results indicate that HA2 stands as the most promising conserved IAV AG for universal vaccine development.
- Keywords
- dendritic cells, human, influenza, routes of administration, swine, vaccine,
- Publication type
- Journal Article MeSH