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Indoor Air Quality (IAQ) is strongly associated with animal health and wellbeing. To identify possible problems of the indoor environment of macaques (Macaca spp.), we assessed the IAQ. The temperature (°C), relative humidity (%) and concentrations of inhalable dust (mg/m3), endotoxins (EU/m3), ammonia (ppm) and fungal aerosols were measured at stationary fixed locations in indoor enclosures of group-housed rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). In addition, the personal exposure of caretakers to inhalable dust and endotoxins was measured and evaluated. Furthermore, the air circulation was assessed with non-toxic smoke, and the number of times the macaques sneezed was recorded. The indoor temperature and relative humidity for both species were within comfortable ranges. The geometric mean (GM) ammonia, dust and endotoxin concentrations were 1.84 and 0.58 ppm, 0.07 and 0.07 mg/m3, and 24.8 and 6.44 EU/m3 in the rhesus and cynomolgus macaque units, respectively. The GM dust concentrations were significantly higher during the daytime than during the nighttime. Airborne fungi ranged between 425 and 1877 CFU/m3. Personal measurements on the caretakers showed GM dust and endotoxin concentrations of 4.2 mg/m3 and 439.0 EU/m3, respectively. The number of sneezes and the IAQ parameters were not correlated. The smoke test revealed a suboptimal air flow pattern. Although the dust, endotoxins and ammonia were revealed to be within accepted human threshold limit values (TLV), caretakers were exposed to dust and endotoxin levels exceeding existing occupational reference values.

Additional file 1: Figure S 1. Composition of workshop participants as per field of expertise. The organizing team mainly consists of meta-researchers with a clinical or preclinical background. Other refers to e.g., stakeholders from funding agencies that also attended the workshop. Methods S1. Multi-stakeholder workshop method-Workshop design. Glossary. Glossary of terms.

Objective To investigate the clinical and physiological effects of intravenous (IV) alfaxalone alone or in combination with buprenorphine, butorphanol or tramadol premedication in marmosets. Study design Prospective, randomized, blinded, crossover design. Animals Nine healthy marmosets (391 ± 48 g, 3.7 ± 2.2 years old). Methods Meloxicam 0.20 mg kg−1 subcutaneously, atropine 0.05 mg kg−1 intramuscularly (IM) and either buprenorphine 20 μg kg−1 IM (BUP-A), butorphanol 0.2 mg kg−1 IM (BUT-A), tramadol 1.5 mg kg−1 IM (TRA-A) or no additional drug (control) were administered to all marmosets as premedication. After 1 hour, anaesthesia was induced with 16 mg kg−1 alfaxalone IV. All animals received all protocols. The order of protocol allocation was randomized with a minimum 28 day wash-out period. During anaesthesia, respiratory and pulse rates, rectal temperature, haemoglobin oxygen saturation, arterial blood pressure, palpebral and pedal withdrawal reflexes and degree of muscle relaxation were assessed and recorded every 5 minutes. Quality of induction and recovery were assessed. Duration of induction, immobilization and recovery were recorded. Blood samples were analysed for aspartate aminotransferase, creatine kinase and lactate dehydrogenase concentrations. The protocols were compared using paired t tests, Wilcoxon's signed-rank test with Bonferroni's corrections and linear mixed effect models where appropriate. Results Out of nine animals, apnoea was noted in eight animals administered protocol BUP-A and two animals administered protocol BUT-A. With TRA-A and control protocols, apnoea was not observed. No other significant differences in any of the parameters were found; however, low arterial blood pressures and hypoxia occurred in TRA-A. Conclusions and clinical relevance Our study employing different premedications suggests that the previously published dose of 16 mg kg−1 alfaxalone is too high when used with premedication because we found a high incidence of complications including apnoea (BUP-A), hypotension and hypoxaemia (TRA-A). Appropriate monitoring and countermeasures are recommended.

The present invention relates to vaccine compositions comprising at least three variants of a subtype of an influenza A and/or B virus antigen, wherein the at least three variants are selected on the basis of differences between their amino acid sequences. The present invention further relates to said vaccine compositions for use in a method of generating an immune response against influenza viruses. Further provided is a method for producing said vaccine compositions.

The development of broadly reactive influenza vaccines raises the need to identify the most appropriate immunoassays that can be used for the evaluation of so-called universal influenza vaccines and to explore a path towards the standardisation of such assays. More than fifty experts from the global influenza vaccine research and development field met to initiate such discussion at a workshop co-organised by the EDUFLUVAC consortium, a European Union funded project coordinated by the European Vaccine Initiative, and the National Institutes of Health/National Institute of Allergy and Infectious Diseases, USA. The workshop audience agreed that it was not possible to establish a single immunoassay for "universal" influenza vaccines because the current approaches differ in the vaccines' nature and immunogenicity properties. Therefore, different scientific rationales for the immunoassay selection are required. To avoid dilution of efforts, the choice of the primary evaluation criteria (eg serological assays or T-cell assays) should drive the effort of harmonisation. However, at an early phase of clinical development, more efforts on exploratory assessments should be undertaken to better define the immune profile in response to immunisation with new vaccines. The workshop concluded that each laboratory should aim towards validation of the appropriate immunoassays used during the entire process of vaccine development from antigen discovery up to establishment of correlates of protection, including the different steps of quality control (eg potency assays), animal studies and human clinical development. Standardisation of the immunoassays is the ultimate goal, and there is a long way to go.