Safety and immunogenicity of a novel multiple antigen pneumococcal vaccine in adults: A Phase 1 randomised clinical trial

BACKGROUND: Pneumococcal vaccines, combining multiple protein antigens, provide an alternative approach to currently marketed vaccines and may provide broader protection against pneumococcal disease. This trial evaluated the safety and immunogenicity of a novel vaccine candidate PnuBioVax in healthy young adults. METHODS: In a Phase 1 double-blind study, 36 subjects (18–40 years) were randomised to receive 3 doses of PnuBioVax, 28 days apart, at one of three dose levels (50, 200, 500 µg) or placebo. Safety assessments included rates of emergent adverse events (AEs), injection site and systemic reactions. Immunogenicity endpoints included antibody titre against PnuBioVax and selected pneumococcal antigens. RESULTS: In the placebo (n = 9) and PnuBioVax (n = 27) vaccinated subjects, there were 15 and 72, reported TEAEs, respectively. The majority of TEAEs were classified as common vaccine related AEs. There were no serious AEs. Common vaccine-related AEs occurred in 13 PnuBioVax (48%) and 2 placebo (22%) subjects and were all headaches (mild and moderate). Injection site reactions, mostly pain and tenderness (graded mild or moderate) were reported, in particular in the 200 µg and 500 µg PnuBioVax groups. There were no clinically significant changes in vital signs, ECG or blood chemistries. Subjects receiving the higher dose (200 and 500 μg) demonstrated a greater fold increase in IgG titre compared with the starting dose (50 μg) or the placebo group. The fold-increase was statistically significantly higher for 200 and 500 µg PnuBioVax vs 50 µg PnuBioVax and placebo at each timepoint post-immunisation. Most subjects receiving 200 and 500 µg PnuBioVax demonstrated a ≥2-fold increase in antibody against pneumolysin (Ply), Pneumococcal surface antigen (PsaA), PiaA (Pneumococcal iron acquisition), PspA (Pneumococcal surface protein A) and pilus proteins (RrgB and RrgA). CONCLUSIONS: All dose levels were considered safe and well tolerated. There was a statistically significant increase in anti-PnuBioVax IgG titres at the 200 and 500 µg dose levels compared to 50 µg and placebo. Trial registration number: NCT02572635https://www.clinicaltrials.gov

A novel, multiple-antigen pneumococcal vaccine protects against lethal Streptococcus pneumoniae challenge

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes, and has led to non-vaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp, thought to be immune adjuvants). Proteomics and immunoblots demonstrated that compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognised protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including non-pneumococcal conjugate vaccine serotypes. Homologous and heterologous strains of S. pneumoniae were opsonised after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, whilst passive transfer of rabbit serum from MAV vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologous S. pneumoniae strains. Direct comparison of MAV preparations made with or without the heat-shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection against S. pneumoniae

Reduction of visual acuity decreases capacity to evaluate radiographic image quality

Aim: To determine the impact of reduced visual acuity on the evaluation of a test object and appendicular radiographs. Methods: Visual acuity was reduced by two different magnitudes using simulation glasses and compared to normal vision (no glasses). During phase one phantom images were produced for the purpose of counting objects by 13 observers and on phase 2 image appraisal of anatomical structures was performed on anonymized radiographic images by 7 observers. The monitors were calibrated (SMPTE RP133 test pattern) and the room lighting was maintained at 7 ±1 lux. Image display and data on grading were managed using ViewDEX (v.2.0) and the area under the visual grading characteristic (AUCVGC) was calculated using VGC Analyzer (v1.0.2). Inferential statistics were calculated using SPSS. Results: For the evaluation of appendicular radiographs the total interpretation time was longer when visual acuity was reduced with 2 pairs of simulation glasses (15.4 versus 8.9 min). Visual grading analysis showed that observers can lose the ability to detect anatomical and contrast differences when they have a simulated visual acuity reduction, being more challenging to differentiate low contrast details. No simulation glasses, compared to 1 pair gives an AUCVGC of 0.302 (0.280, 0.333), that decreases to 0.197 (0.175, 0.223) when using 2 pairs of glasses. Conclusions: Reduced visual acuity has a significant negative impact on the evaluation of test objects and clinical images. Further work is required to test the impact of reduced visual acuity on visual search, technical evaluation of a wider range of images as well as pathology detection/characterization performance

Immunogenicity and mechanisms of action of PnuBioVax, a multi-antigen serotype-independent prophylactic vaccine against infection with Streptococcus pneumoniae

Streptococcus pneumoniae has multiple protein antigens on the surface in addition to the serotype specific polysaccharide capsule antigen. Whilst the capsule antigen is the target of the polysaccharide vaccines, bacterial proteins can also act as targets for the immune system. PnuBioVax (PBV) is being developed as a multi-antigen, serotype-independent prophylactic vaccine against S. pneumoniae disease. In this study we have sought to elucidate the immune response to PBV in immunised rabbits. Sera from PBV immunised rabbits contained high levels of IgG antibodies to the PBV vaccine, and pneumococcal antigens PspA, Ply, PsaA and PiuA which are components of PBV, when compared with control sera. The PBV sera supported killing of the vaccine strain TIGR4 in an opsonophagocytic killing assay and heterologous strains 6B, 19F and 15B. In addition, incubation in PBV sera led to agglutination of several strains of pneumococci, inhibition of Ply-mediated lysis of erythrocytes and reduced bacterial invasion of lung epithelial cells in vitro. These data suggest that PBV vaccination generates sera that has multiple mechanisms of action that may provide effective protection against pneumococcal infection and give broader strain coverage than the current polysaccharide based vaccines

What constitutes effective governance of recreational fisheries?—A global review

The effectiveness of recreational fisheries governance has been mixed, with some countries boasting good governance practices that sustain productive recreational fisheries, while others lack any policies and governance structures specific to recreational fisheries. Here, we identify what constitutes effective governance of recreational fisheries by carrying out: (a) a desktop review of 227 country-specific fisheries legislation, policies and strategies; and (b) a follow-up questionnaire-based survey covering 57 contacts in 29 selected countries. Our results show that while recreational fishing is referred to in the main legislation of 67% of the countries reviewed, only 86 of these 152 countries provide a definition for either “recreational” or “sport” fishing and not always in the main legislation. Recreational fisheries are not considered to be effectively managed in many countries, with less than a quarter of respondents claiming that management in their country is effective. Furthermore, the management efficacy, including compliance with regulations, was considered greater for the industrial and small-scale fishing sectors than for recreational fisheries in most countries. From our findings, it appears that effective recreational fisheries governance requires explicit acknowledgement of recreational fisheries with a clear legal definition in Policy, a well-developed Policy statement, extensive co-management processes, clearly defined biological, economic and social monitoring structures and efficient and transparent cost recovery mechanisms. To ensure adaptation to rapidly changing conditions, policy should recognize all fishery sectors and proactively incorporate adaptive planning and contingency plans to effectively secure the diverse values of resources for all users