A comparison of viral microneutralization and haemagglutination inhibition assays as measures of seasonal inactivated influenza vaccine immunogenicity in the first year after reduced intensity conditioning, lymphocyte depleted allogeneic haematopoietic stem cell transplant

Traditionally, immune response to influenza vaccines has been measured using the haemagglutination inhibition (HAI) assay. A broader repertoire of techniques including the sensitive viral microneutralization (VMN) assay is now recommended by the European Medicines Agency (EMA). Comparing HAI and VMN, we determined immune response to a trivalent 2015–2016 seasonal inactivated influenza vaccine (SIIV) administered to 28 recipients of allogeneic haematopoietic stem cell transplant (HSCT). Vaccination was within the first-year post-transplant at a median of 78.5 (24–363) days. The proportion of patients with baseline and post-vaccination HAI titres ≥ 1:40 were 28.6% and 25% for A(H1N1)pdm09, 14.3% at both timepoints for A(H3N2), and 32.1% and 25% for B(Phuket). Pre and Post-vaccination geometric mean titres(GMT) were higher by VMN than HAI for A(H1N1)pdm09 and A(H3N2), but lower for B(Phuket)(p= 0.05) for all components. A single seroconversion to A(H1N1) was detected by ELISA-VMN. None of patient age, lymphocyte count, days from transplant to vaccination, donor type, or graft-versus-host disease (GVHD) or immunosuppressive therapy (IST) at vaccination correlated with baseline or post-vaccination titres by either assay. This absence of seroresponse to SIIV in the first-year post HSCT highlights the need for novel immunogenic vaccination formulations and schedules in this high-risk population

Diversity of Lecidea (Lecideaceae, Ascomycota) species revealed by molecular data and morphological characters

The diversity of lichens, especially crustose species, in continental Antarctica is still poorly known. To overcome difficulties with the morphology based species delimitations in these groups, we employed molecular data (nuclear ITS and mitochondrial SSU rDNA sequences) to test species boundaries within the genus Lecidea. Sampling was done along a north–south transect at five different areas in the Ross Sea region (Cape Hallett, Botany Bay to Mount Suess, Taylor Valley, Darwin Area and Mount Kyffin). A total of 153 specimens were collected from 13 localities. Phylogenetic analyses also include specimens from other regions in Antarctica and non-Antarctic areas. Maximum parsimony, maximum likelihood and Bayesian analyses agreed in placing the samples from continental Antarctica into four major groups. Based on this phylogenetic estimate, we restudied the micromorphology and secondary chemistry of these four clades to evaluate the use of these characters as phylogenetic discriminators. These clades are identified as the following species Lecidea cancriformis, L. andersonii as well as the new species L. polypycnidophora Ruprecht & Türk sp. nov. and another previously unnamed clade of uncertain status, referred to as Lecidea sp. (L. UCR1)

TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors

Despite the promising efficacy of adoptive cell therapies (ACT) in melanoma, complete response rates remain relatively low and outcomes in other cancers are less impressive. The immunosuppressive nature of the tumor microenvironment and the expression of immune-inhibitory ligands, such as PD-L1/CD274 by the tumor and stroma are considered key factors limiting efficacy. The addition of checkpoint inhibitors (CPI) to ACT protocols bypasses some mechanisms of immunosuppression, but associated toxicities remain a significant concern. To overcome PD-L1–mediated immunosuppression and reduce CPI-associated toxicities, we used TALEN technology to render tumor-reactive T cells resistant to PD-1 signaling. Here, we demonstrate that inactivation of the PD-1 gene in melanoma-reactive CD8+ T cells and in fibrosarcoma-reactive polyclonal T cells enhanced the persistence of PD-1 gene-modified T cells at the tumor site and increased tumor control. These results illustrate the feasibility and potency of approaches incorporating advanced gene-editing technologies into ACT protocols to silence immune checkpoints as a strategy to overcome locally active immune escape pathways

Multi-species sociology of the body

The human body has become a central focus in sociology. Such work has centred largely on the human body and its significance in social contexts. This article draws on sociological understandings of human embodiment, especially the idea of the ‘body as a project’, to facilitate a multi-species understanding of bodies and their entanglements. Conceptualising the body as a project has provided sociological insights into the scientific and technological innovations that are designed to improve health and delay death. Nonhuman animals are entangled in these efforts, though their presence is often occluded. By examining notions of body masks, body regimes and body options, which are well established in sociological thinking about the body, this article seeks to prompt consideration of how to utilise theories of the body to examine human–nonhuman animal entanglements in order to establish a multi-species sociology of the body

Harm–benefit analysis – what is the added value?:A review of alternative strategies for weighing harms and benefits as part of the assessment of animal research

Animal experiments are widely required to comply with the 3Rs, to minimise harm to the animals and to serve certain purposes in order to be ethically acceptable. Recently, however, there has been a drift towards adding a so-called harm-benefit analysis as an additional requirement in assessing experiments. According to this, an experiment should only be allowed if there is a positive balance when the expected harm is weighed against the expected benefits. This paper aims to assess the added value of this requirement. Two models, the discourse model and the metric model, are presented. According to the former, the weighing of harms and benefits must be conducted by a committee in which different stakeholders engage in a dialogue. Research into how this works in practice, however, shows that in the absence of an explicit and clearly defined methodology, there are issues about transparency, consistency and fairness. According to the metric model, on the other hand, several dimensions of harms and benefits are defined beforehand and integrated in an explicit weighing scheme. This model, however, has the problem that it makes no real room for ethical deliberation of the sort committees undertake, and it has therefore been criticised for being too technocratic. Also, it is unclear who is to be held accountable for built-in ethical assumptions. Ultimately, we argue that the two models are not mutually exclusive and may be combined to make the most of their advantages while reducing the disadvantages of how harm-benefit analysis in typically undertaken

Societal sentience: constructions of the public in animal research policy and practice

The use of non-human animals as models in research and drug testing is a key route through which contemporary scientific knowledge is certified. Given ethical concerns, regulation of animal research promotes the use of less ‘sentient’ animals. This paper draws on a documentary analysis of legal documents, and qualitative interviews with Named Veterinary Surgeons and others at a commercial laboratory in the UK. Its key claim is that the concept of animal sentience is entangled with a particular imaginary of how the general public or wider society views animals. We call this imaginary societal sentience. Against a backdrop of increasing ethnographic work on care encounters in the laboratory, this concept helps to stress the wider context within which such encounters take place. We conclude that societal sentience has potential purchase beyond the animal research field, in helping to highlight the affective dimension of public imaginaries (Welsh and Wynne 2013), and their ethical consequences. Researching and critiquing societal sentience, we argue, may ultimately have more impact on the fate of humans and non-humans in the laboratory, than focusing wholly on ethics as situated practice