How do you choose a book for a pre-arrival shared reading scheme within a University? A case study

This paper continues the exploration of Kingston University’s pre-arrival shared reading scheme, the Kingston University Big Read (KUBR), this time considering action research into how best to choose a common book. After a review of methods used to choose books both specifically in American universities and generally within large shared reading groups, the method used for the KUBR is described. A key objective of the KUBR is to promote inclusion, so the longlist of titles considered was produced by inviting the entire community to submit suggestions. Since the list was extensive, time to make a choice was short, and there was a strong desire for the methodology to be as objective as possible, it was decided to identify the key criteria relevant to choosing a suitable book and then use a simple algorithm—essentially a weighted scoring system—to score each book using readily available data in order to make a shortlist of six books. These were then read by a panel of students and administrative and academic staff. The book finally chosen was Matt Haig’s The Humans. This paper details each step of the method and finishes with an appraisal and lessons learnt for next time.</jats:p

Constraining the Orbit and Mass of epsilon Eridani b with Radial Velocities, Hipparcos IAD-Gaia DR2 Astrometry, and Multiepoch Vortex Coronagraphy Upper Limits

ϵ Eridani is a young planetary system hosting a complex multibelt debris disk and a confirmed Jupiter-like planet orbiting at 3.48 au from its host star. Its age and architecture are thus reminiscent of the early Solar System. The most recent study of Mawet et al., which combined radial-velocity data and Ms-band direct imaging upper limits, started to constrain the planet's orbital parameters and mass, but are still affected by large error bars and degeneracies. Here we make use of the most recent data compilation from three different techniques to further refine ϵ Eridani b's properties: RVs, absolute astrometry measurements from the Hipparcos and Gaia missions, and new Keck/NIRC2 Ms-band vortex coronagraph images. We combine this data in a Bayesian framework. We find a new mass, ${M}_{b}={0.66}_{-0.09}^{+0.12}$ M[SUB]Jup[/SUB], and inclination, $i=78.{81}_{-22.41\mathop{}\limits^{^\circ }}^{+29.34}$ , with at least a factor 2 of improvement over previous uncertainties. We also report updated constraints on the longitude of the ascending node, the argument of the periastron, and the time of periastron passage. With these updated parameters, we can better predict the position of the planet at any past and future epoch, which can greatly help define the strategy and planning of future observations and with subsequent data analysis. In particular, these results can assist the search for a direct detection with JWST and the Nancy Grace Roman Space Telescope's coronagraph instrument.EPIC; NNEx

Replication-competent Vectors and Empty Virus-like Particles: New Retroviral Vector Designs for Cancer Gene Therapy or Vaccines

Replication-defective vectors based on murine oncoretroviruses were the first gene transfer vectors to be used in successful gene therapies. Despite this achievement, they have two major drawbacks: insufficient efficacy for in vivo gene transfer and insertional mutagenesis. Attempts to overcome these problems have led to two retroviral vector designs of principally opposite character: replication-competent vectors transducing largely intact genomes and genome-free vectors. Replication-competent retroviral vectors have achieved dramatically improved efficacy for in vivo cancer gene therapy and genome-free retroviral vectors expressing different kinds of antigens have proven excellent as immunogens. Current developments aim to improve the safety of the replication-competent vectors and to augment the production efficiency of the genome-free vectors by expression from heterologous viral or non-viral vectors. Together with the continuous advances of classical defective retroviral vectors for ex vivo gene therapy, these developments illustrate that, due to their tremendous design versatility, retroviral vectors remain important vectors for gene therapy applications

Beyond oncolytic virotherapy: replication-competent retrovirus vectors for selective and stable transduction of tumors

As cancer gene therapy employing replication-defective vectors has met with limited clinical success, there is renewed interest in using replication-competent viruses for oncolytic virotherapy. In preclinical and clinical studies, various attenuated vaccine strains and engineered virus vectors are currently being tested for their ability to achieve tumor-selective cell killing. However, significant improvements are still required in tumor selectivity, cytolytic potency, and modulating immune responses to achieve anti-tumor effects without prematurely terminating virus spread. Recently, we have developed murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors for highly efficient, selective, and persistent gene transfer to cancer cells, and found that such vectors may offer significant advantages as oncolytic agents. In a variety of preclinical models, RCR vectors can achieve efficient and persistent gene delivery as the virus replicates throughout an entire tumor mass after inoculation with initial multiplicities of infection as low as 0.001. When engineered to deliver suicide genes, RCR vectors achieve highly efficient and synchronized cell killing triggered by pro-drug administration, both in culture and in tumor models in vivo. Further strategies are being explored to enhance the packaging capacity, efficiency, and specificity of this vector system through the development of semi-replicative RCR vectors, adenovirus-RCR hybrids, and incorporation of tumor targeting mechanisms via modification of binding tropism and transcriptional regulation. In addition, the ability of these vectors to achieve stable transgene expression in infected tumor cells may allow therapeutic applications that move beyond oncolysis per se

Recombinant retrovirus-like particle forming DNA vaccines in prime-boost immunization and their use for hepatitis C virus vaccine development.

International audienceBACKGROUND: The expression of Moloney murine leukemia virus (Mo-MLV) gag proteins is sufficient to generate retrovirus-like particles (retroVLPs) that can be used as antigen-display platforms by pseudotyping with heterologous envelope proteins or by insertion of epitopes in structural constituents. To circumvent the in vitro production of such retroVLPs, we used DNA plasmids generating recombinant retroVLPs (plasmo-retroVLPs) as immunogens. We previously demonstrated that plasmo-retroVLPs induce significantly better antigen-specific T cell responses and antiviral immune protection than plasmids bearing a single mutation preventing retroVLPs assembly. In the present study, we investigated the possibility of using such plasmo-retroVLPs in prime-boost immunization strategies for hepatitis C virus (HCV) vaccine development. METHODS: To define the best immunization regimen with plasmo-retroVLPs and serotype 5 recombinant adenovirus vectors (rAd5), we used standardized methodologies measuring immune responses to the GP(33-41) 'gold standard' antigen. The protective efficacy of these immunization schedules was also evaluated in mice after tumor challenge. We then applied the optimal prime-boost immunization strategy using vectors expressing HCV-E1/E2 envelope glycoproteins. RESULTS: Using vectors expressing the model antigen, we demonstrated that rAd5(GP33-41)/plasmo-retroVLP(GP33-41) regimen induced significantly higher cellular immune responses than plasmo-retroVLP(GP33-41)/rAd5(GP33-41). Consequently, HCV-specific plasmo-retroVLPs (plasmo-retroVLP(E1E2)) were used as boost in mice primed with rAd5(E1E2) and we observed that plasmo-retroVLP(E1E2) significantly increased E1/E2-specific interferon-gamma cellular responses and E2-specific antibody generation. By contrast, plasmids unable to form E1/E2-pseudotyped retroVLPs had no boosting effect, revealing the importance of presenting E1/E2 in a particulate form. CONCLUSIONS: Altogether, combining plasmo-retroVLPs that represent a new class of genetic vaccines in a heterologous prime-boost vaccination strategy appears to be a promising strategy for HCV vaccine development

DNA vaccines expressing retrovirus-like particles are efficient immunogens to induce neutralizing antibodies.

International audienceWe aimed at improving DNA vaccination efficiency for inducing neutralizing antibodies. We used plasmids encoding Gag of MLV and envelope proteins of VSV or WNV. Upon in vivo injection, they generate retrovirus-derived VLPs pseudotyped with these envelopes expressed in their wild-type conformation. We show that these plasmo-retroVLPs induce potent humoral responses, the efficacy of which could be improved by co-administration of DNA encoding adjuvant cytokines. Antibodies against VSV or WNV were detected earlier than with plasmids not generating VLPs, and had higher neutralizing activities. These results highlight the potential of this approach for vaccination strategies aiming at neutralizing antibody induction

Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B antigen induces antibodies with potent and broad neutralizing activity.

A prophylactic vaccine to prevent the congenital transmission of human cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in immunosuppressed recipients of HCMV-infected solid organ transplants is highly desirable. Neutralizing antibodies against HCMV confer significant protection against infection, and glycoprotein B (gB) is a major target of such neutralizing antibodies. However, one shortcoming of past HCMV vaccines may have been their failure to induce high-titer persistent neutralizing antibody responses that prevent the infection of epithelial cells. We used enveloped virus-like particles (eVLPs), in which particles were produced in cells after the expression of murine leukemia virus (MLV) viral matrix protein Gag, to express either full-length CMV gB (gB eVLPs) or the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV)-G protein (gB-G eVLPs). gB-G-expressing eVLPs induced potent neutralizing antibodies in mice with a much greater propensity toward epithelial cell-neutralizing activity than that induced with soluble recombinant gB protein. An analysis of gB antibody binding titers and T-helper cell responses demonstrated that high neutralizing antibody titers were not simply due to enhanced immunogenicity of the gB-G eVLPs. The cells transiently transfected with gB-G but not gB plasmid formed syncytia, consistent with a prefusion gB conformation like those of infected cells and viral particles. Two of the five gB-G eVLP-induced monoclonal antibodies we examined in detail had neutralizing activities, one of which possessed particularly potent epithelial cell-neutralizing activity. These data differentiate gB-G eVLPs from gB antigens used in the past and support their use in a CMV vaccine candidate with improved neutralizing activity against epithelial cell infection

Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B antigen induces antibodies with potent and broad neutralizing activity.

A prophylactic vaccine to prevent the congenital transmission of human cytomegalovirus (HCMV) in newborns and to reduce life-threatening disease in immunosuppressed recipients of HCMV-infected solid organ transplants is highly desirable. Neutralizing antibodies against HCMV confer significant protection against infection, and glycoprotein B (gB) is a major target of such neutralizing antibodies. However, one shortcoming of past HCMV vaccines may have been their failure to induce high-titer persistent neutralizing antibody responses that prevent the infection of epithelial cells. We used enveloped virus-like particles (eVLPs), in which particles were produced in cells after the expression of murine leukemia virus (MLV) viral matrix protein Gag, to express either full-length CMV gB (gB eVLPs) or the full extracellular domain of CMV gB fused with the transmembrane and cytoplasmic domains from vesicular stomatitis virus (VSV)-G protein (gB-G eVLPs). gB-G-expressing eVLPs induced potent neutralizing antibodies in mice with a much greater propensity toward epithelial cell-neutralizing activity than that induced with soluble recombinant gB protein. An analysis of gB antibody binding titers and T-helper cell responses demonstrated that high neutralizing antibody titers were not simply due to enhanced immunogenicity of the gB-G eVLPs. The cells transiently transfected with gB-G but not gB plasmid formed syncytia, consistent with a prefusion gB conformation like those of infected cells and viral particles. Two of the five gB-G eVLP-induced monoclonal antibodies we examined in detail had neutralizing activities, one of which possessed particularly potent epithelial cell-neutralizing activity. These data differentiate gB-G eVLPs from gB antigens used in the past and support their use in a CMV vaccine candidate with improved neutralizing activity against epithelial cell infection