Genome sequences of four cluster P mycobacteriophages

Four bacteriophages infecting Mycobacterium smegmatis mc2155 (three belonging to subcluster P1 and one belonging to subcluster P2) were isolated from soil and sequenced. All four phages are similar in the left arm of their genomes, but the P2 phage differs in the right arm. All four genomes contain features of temperate phages

Adaptation as Literary Analysis

Panel Chair: Gretchen Busl, TW

Safety and Immunogenicity of Pfs25-EPA/Alhydrogel^®, a Transmission Blocking Vaccine against <i>Plasmodium falciparum</i>: An Open Label Study in Malaria Naïve Adults

<div><p>Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from <i>Pseudomonas aeruginosa</i>. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel^®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4^th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel^® in a malaria-endemic population.</p></div

Immunofluorescence assays with immune sera.

<p>A. Surface labeling of zygotes with sera from one volunteer (#20) collected on days 0, 314 and 356, with Pfs25 specific mouse mAbs 1G2 and 4B7. B. Recognition of parasite protein in fixed ookinetes with sera from one volunteer (#20) collected on days 0, 314 and 356, with Pfs25 specific mouse mAb 4B7. Magnification 1000X.</p

Summary of adverse events after each vaccination.

<p>Clinical solicited (A-C) and Laboratory (D-F) adverse events after each vaccination with each dose group are reported in individual graphs: Group 1a (A and D), 1b (B and E) and Group 2 (C and F). All adverse events were mild except when indicated as moderate.</p

Study flow chart.

<p>Thirty (30) participants were enrolled, 23 completed the study per protocol.</p

Anti-Pfs25 responses.

<p>A, Groups 1a and 1b participants, receiving conjugated proteins comprising of 8 μg and 16 μg Pfs25H, respectively. B, Group 2 participants, receiving 47 μg Pfs25H. Arrows indicate the day of vaccination. Closed circles represent antibody level and individual participants, and black bars indicate geometric mean of antibody levels and t-distribution 95% confidence interval (CI).</p

Transmisison reducing activity of immune sera.

<p>A. Transmission reducing activity of sera collected 2 weeks after each initial vaccination and 8 weeks after the booster vaccination. Each data point represents the average of two results in the SMFA, and lines indicate estimate EC50 and point-wise confidence interval by GEE model. B. Standard deviation (SD) of individual TRA from replica assays. Thick blue line indicates the threshold representing significant biological activity (50% TRA), the black line is a standard loess smooth curve. The green, red, blue, and black dots correspond to the data points on D70, D134, D314 (2 weeks after the second, third, and fourth vaccination respectively), and D356 (8 weeks after the fourth vaccination), as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163144#pone.0163144.g004" target="_blank">Fig 4A</a>.</p