Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection leads to a robust induction of MICA mRNA expression, however the subsequent surface expression is potently hindered. Thus, VSV lines up with human cytomegalovirus (HCMV) and adenovirus, which actively subvert the immune system by negatively affecting NKG2D-ligand surface expression. VSV infection caused an active suppression of NKG2D-ligand surface expression, affecting both endogenous and histone deacetylase (HDAC)-inhibitor induced MICA, MICB and ULBP-2 expression. The classical immune escape mechanism of VSV (i.e., the M protein blockade of nucleocytoplasmic mRNA transport) was not involved, as the VSV mutant strain, VSVΔM51, which possess a defective M protein, prevented MICA surface expression similarly to wild-type VSV. The VSV mediated down modulation of NKG2D-ligand expression did not involve apoptosis. Constitutive expression of MICA bypassed the escape mechanism, suggesting that VSV affect NKG2D-ligand expression at an early post-transcriptional level. Our results show that VSV possess an escape mechanism, which could affect the immune recognition of VSV infected cancer cells. This may also have implications for immune recognition of cancer cells after combined treatment with VSV and chemotherapeutic drugs

CAF01 Potentiates Immune Responses and Efficacy of an Inactivated Influenza Vaccine in Ferrets

Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6′-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Smoke and Mirrors: Opportunity and Aspiration in 14-19 Education

The policy discourse around those young people who are the focus of the 14-19 agenda is one of negativity which, in its use of language such as non-academic, disaffected, disadvantaged places young people firmly within a deficit model. This model frames these young people as low achievers with low aspirations, routinely dismisses them as non-academic yet claims to offer opportunities in the form of a vocational education which, according to the rhetoric, will lead to a lifelong (nirvana?) of high skill, high paid work, personal satisfaction and opportunity (providing they continue to engage in lifelong learning), something which many young people take on trust. Drawing on original empirical research, and working within a framework informed by Marxist and social justice concepts, this paper contests the assumption that these young people have low aspirations, arguing that falling within a deficit model, constrained by discourses of negativity, powerless to change a system which militates against them and lacking the agency for change their chances of achieving those aspirations are almost non-existent. The paper poses a number of questions: What are 'high' and 'low' aspirations? What is 'non ? academic'? Why, every year, are nearly half of all young people characterized in this way? What is, or is not, an 'opportunity'? It argues that notions of opportunity are, in fact, smoke and mirrors, a massive deception which enables the channelling of these young people into the low pay, low skill work market in readiness to fulfil government demands for cheap labour as and when it is needed. Finally, it concludes with proposals for change in the 14-19 and PCET systems which could provide a more equitable and effective framework for young people to achieve their hopes and dreams