Widespread support for a global species list with a formal governance system.

Taxonomic data are a scientific common. Unlike nomenclature, which has strong governance institutions, there are currently no generally accepted governance institutions for the compilation of taxonomic data into an accepted global list. This gap results in challenges for conservation, ecological research, policymaking, international trade, and other areas of scientific and societal importance. Consensus on a global list and its management requires effective governance and standards, including agreed mechanisms for choosing among competing taxonomies and partial lists. However, governance frameworks are currently lacking, and a call for governance in 2017 generated critical responses. Any governance system to which compliance is voluntary requires a high level of legitimacy and credibility among those by and for whom it is created. Legitimacy and credibility, in turn, require adequate and credible consultation. Here, we report on the results of a global survey of taxonomists, scientists from other disciplines, and users of taxonomy designed to assess views and test ideas for a new system of taxonomic list governance. We found a surprisingly high degree of agreement on the need for a global list of accepted species and their names, and consistent views on what such a list should provide to users and how it should be governed. The survey suggests that consensus on a mechanism to create, manage, and govern a single widely accepted list of all the world's species is achievable. This finding was unexpected given past controversies about the merits of list governance.

Principles for creating a single authoritative list of the world's species.

Lists of species underpin many fields of human endeavour, but there are currently no universally accepted principles for deciding which biological species should be accepted when there are alternative taxonomic treatments (and, by extension, which scientific names should be applied to those species). As improvements in information technology make it easier to communicate, access, and aggregate biodiversity information, there is a need for a framework that helps taxonomists and the users of taxonomy decide which taxa and names should be used by society whilst continuing to encourage taxonomic research that leads to new species discoveries, new knowledge of species relationships, and the refinement of existing species concepts. Here, we present 10 principles that can underpin such a governance framework, namely (i) the species list must be based on science and free from nontaxonomic considerations and interference, (ii) governance of the species list must aim for community support and use, (iii) all decisions about list composition must be transparent, (iv) the governance of validated lists of species is separate from the governance of the names of taxa, (v) governance of lists of accepted species must not constrain academic freedom, (vi) the set of criteria considered sufficient to recognise species boundaries may appropriately vary between different taxonomic groups but should be consistent when possible, (vii) a global list must balance conflicting needs for currency and stability by having archived versions, (viii) contributors need appropriate recognition, (ix) list content should be traceable, and (x) a global listing process needs both to encompass global diversity and to accommodate local knowledge of that diversity. We conclude by outlining issues that must be resolved if such a system of taxonomic list governance and a unified list of accepted scientific names generated are to be universally adopted.

Reduction in HbA1c using professional flash glucose monitoring in insulin-treated type 2 diabetes patients managed in primary and secondary care settings: A pilot, multicentre, randomised controlled trial.

AIM: Analyse the effects of professional flash glucose monitoring system (FreeStyle Libre Pro™) on glycaemic control in insulin-treated type 2 diabetes. METHODS: Primary (n = 17) and secondary care centres (n = 5) randomised 148 type 2 diabetes patients into three groups: (A) self-monitoring of blood glucose (n = 52), (B) self-monitoring of blood glucose and two Libre Pro sensor wears (n = 46) or (C) self-monitoring of blood glucose and four sensor wears (n = 50). Primary endpoint was time in range (glucose 3.9-10 mmol/L) within group C comparing baseline with days 172-187. Predefined secondary endpoints included HbA1c, hypoglycaemia and quality of life measures analysed within and between groups (clinicaltrials.gov, NCT02434315). RESULTS: In group C, time in range in the first 14 days (baseline) and days 172-187 was similar at 15.0 ± 5.0 and 14.1 ± 4.7 h/day (mean ± SD), respectively, (p = 0.1589). In contrast, HbA1c reduced from baseline to study end within group C by 4.9 ± 8.8 mmol/mol (0.44% ± 0.81%; p = 0.0003). HbA1c was also lower in group C compared with A at study end by 5.4 ± 1.79 mmol/mol (0.48% ± 0.16%; p = 0.0041, adjusted mean ± SE), without increased time in hypoglycaemia (p = 0.1795). Treatment satisfaction scores improved in group C compared with A (p = 0.0225) and no device-related serious adverse events were reported. CONCLUSIONS: Libre Pro can improve HbA1c and treatment satisfaction without increasing hypoglycaemic exposure in insulin-treated type 2 diabetes individuals managed in primary/secondary care centres.

Delivery of a multivalent scrambled antigen vaccine induces broad spectrum immunity and protection against tuberculosis.

The development of effective anti-Tuberculosis (TB) vaccines is an important step towards improved control of TB in high burden countries. Subunit vaccines are advantageous in terms of safety, particularly in the context of high rates of HIV co-infection, but they must contain sufficient Mycobacterium tuberculosis antigens to stimulate immunity in genetically diverse human populations. We have used a novel approach to develop a synthetic scrambled antigen vaccine (TB-SAVINE), comprised of overlapping, recombined peptides from four M. tuberculosis proteins, Ag85B, ESAT-6, PstS3 and Mpt83, each of which is immunogenic and protective against experimental TB. This polyvalent TB-SAVINE construct stimulated CD4 and CD8T cell responses against the individual proteins and M. tuberculosis in C57BL/6 and Balb/c mice, when delivered as DNA, Fowl Pox Virus or Vaccinia Virus vaccines. In addition, the DNA-TBS vaccine induced protective immunity against pulmonary M. tuberculosis infection in C57BL/6 mice. Co-immunization of Balb/c mice with virally expressed TBS and HIV1-SAVINE vaccine stimulated strong T cell responses to both the M. tuberculosis and HIV proteins, indicating no effects of antigenic competition. Further development of this TB-SAVINE vaccine expressing components from multiple M. tuberculosis proteins may prove an effective vaccine candidate against TB, which could potentially form part of a safe, combined preventative strategy together with HIV immunisations.

Novel approach to the formulation of an Epstein-Barr virus antigen-based nasopharyngeal carcinoma vaccine.

Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.

Fowlpox virus vaccines for HIV and SHIV clinical and pre-clinical trials.

DNA prime and recombinant fowlpox virus (rFPV) boost vaccines were designed to express multiple HIV or SIV antigens for use in human clinical trials and in pre-clinical trials in macaques. Three sets of vaccines with matching HIV or SIV antigen sets, modified for vaccine safety considerations, were constructed and shown to express the relevant proteins. The rFPV vaccines with inserts at up to three sites, were stable on passage in chick cell culture, including during GMP manufacture of vaccines for human Phase I clinical trials. Cellular and humoral immunogenicity in mice was demonstrated using a DNA prime/rFPV boost and vaccinia virus challenge model. These data establish a preliminary safety and efficacy profile for these multigenic vaccines suggesting they are suitable for advanced development as candidate HIV vaccines.

Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine designed for global use.

Induction of high levels of broadly reactive cytotoxic T lymphocytes (CTL) remains a promising approach for an effective HIV-1 vaccine. We have developed a novel genetic-based vaccine strategy that encodes consensus overlapping peptide sets from all HIV-1 proteins scrambled together. This synthetic scrambled antigen vaccine (SAVINE) strategy has significant advantages, e.g. capacity to encode more antigens safely and is very flexible compared to traditional isolate-based strategies. The SAVINE vaccine strategy is clearly immunogenic, being able to restimulate a range of human HIV-1 specific responses in vitro and induce HIV-1 specific immunity in vivo in mice. Interestingly, different in vivo delivery strategies affected the resulting immunity and immunodominance pattern in mice. This platform strategy could be used for other infections and cancers where T cell responses are important for protection.

Prime-boost immunization generates a high frequency, high-avidity CD8(+) cytotoxic T lymphocyte population.

Development and expansion of high-avidity T cell populations may be important for the success of immunization strategies against HIV and other pathogens that have presented major problems for vaccine development. We have used tetrameric-MHC complexes ex vivo and lytic assays to show that 'prime-boost' immunization with DNA vaccines and recombinant poxvirus vectors generates high frequencies of cytotoxic T lymphocytes (CTL) that recognize target cells expressing very low levels of specific antigen. These cells persist for at least 6 months at levels representing approximately 10% of the CD8(+) T cell population. Using a novel in vivo assay, we also found that prime-boost immunized animals were capable of eliminating target cells expressing 10- to 100-fold less immunogenic peptide than mice given either vector alone. In addition, viral challenge led to rapid expansion of CTL effectors in prime-boost groups, to levels representing >30% of total CD8(+) T cell numbers. Strategies that generate specific T cells of high avidity, optimizing early detection of infected cells, offer new hope for effective prophylaxis and immunotherapy.