Development of Typhax, a Salmonella Typhi Vi polysaccharide protein capsular matrix vaccine

Matrivax Research & Development Corporation is researching and developing a novel technology termed Protein Capsular Matrix Vaccine (PCMV) as an alternative to polysaccharide-protein conjugate vaccines. In a PCMV, polysaccharide antigens are entrapped in a cross-linked protein ‘carrier’ matrix. This process is simpler than conjugate vaccines and should yield polysaccharide vaccines that elicit TH-cell ‘memory’, are highly efficacious, and less expensive to manufacture. Typhoid fever, caused by Salmonella enterica serovar Typhi, is a disease that afflicts ~16 million people worldwide, resulting in 600,000 deaths, annually. Although typhoid fever vaccines are commercially available, there are significant limitations. Ty21a is an oral vaccine that requires a multi-dose regimen; whereas Typherix® and TyphimVi® are parenteral and associated with local reactogenicity. The existing typhoid vaccines confer variable, ~70%, protective efficacy, do not protect young children (\u3c2 years old), and are not used for routine immunization. Please click Additional Files below to see the full abstract

Heat shock proteins of vegetative and fruiting Myxococcus xanthus cells

The heat shock response of Myxococcus xanthus was investigated and characterized. When shifted from 28 to 40°C, log-phase cells rapidly ceased growth, exhibited a 50% reduction in CFU, and initiated the synthesis of heat shock proteins (HTPs). Heat-shocked log-phase M. xanthus cells labeled with [35S]methionine were found to produce 18 major HTPs. The HTPs, analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, were characterized with regard to molecular mass, subcellular location (periplasm, membrane, or cytoplasm), and temperature required for expression. Most HTPs were expressed at 36°C, the optimum growth temperature of M. xanthus. Cells preincubated at 36°C for 1 h before being shifted to 40°C demonstrated increased thermotolerance compared with cells shifted directly from 28 to 40°C. The HTPs produced by heat-shocked starvation-induced fruiting cells and glycerol-induced sporulating cells were also analyzed and characterized. Thirteen HTPs were detected in fruiting cells shifted from 28 to 40°C. Six of these HTPs were not seen in vegetative M. xanthus cells. Log-phase cells induced to sporulate by the addition of glycerol produced 17 HTPs after being shifted to 40°C. These HTPs were found to be a mixture of HTPs detected in heat-shocked log-phase cells and heat-shocked fruiting cells

DEVELOPMENT OF PROTEIN CAPSULAR MATRIX VACCINE (PCMV) TECHNOLOGY

Matrivax R&D Corp. is a start-up biotechnology company with R&D operations located in Boston, USA and a vaccine pilot facility in Haikou, China. We are developing a proprietary vaccine process that entraps polysaccharides in a cross-linked protein ‘carrier’ or matrix, termed Protein Capsular Matrix Vaccine (PCMV), as an alternative to conjugate vaccine technology. Despite highly efficacious pneumococcal vaccines such as Prevnar®, S. pneumoniae causes \u3e 1 million deaths worldwide annually. Likewise, typhoid fever afflicts ~16 million people, resulting in 600,000 deaths despite effective vaccines such as Typhim Vi® and Ty21a. The premise is that inexpensive,efficacious polysaccharide vaccines that elicit TH-cell ‘memory’ will actively displace their unconjugated and conjugated vaccine counterparts. Towards this end, Matrivax is actively research and developing pneumococcal, enteric fever, and meningococcal PCMV candidates. In preliminary studies, a pneumococcal capsular polysaccharide (PPS) 14 ‘whole reaction’ PCMV employing ‘unoptimized chemistry’ elicited an anti-PPS14 reciprocal IgG antibody titer of ~7,000. Functional antibodies were elicited as evidenced by anti-sera facilitated opsonization and passively transferred antibodies conferring protection against lethal pneumococcal challenge. Recently Matrivax devised ‘optimized’ PCMV chemical reaction conditions improving polysaccharide incorporation into protein matrices as well as separated ‘whole reaction’ PCMV by size-exclusion chromatography yielding ‘size-fractionated’ PCMV particles. Size fractionated PPS14 PCMVs and Prevnar® were used to immunize mice in a three dose, bi-weekly regimen. Particle sized PCMV containing 0.12 and 0.03 ug PPS14 elicited anti-PPS14 reciprocal antibody GMT of 617,077 and 501,103,respectively, compared to Prevnar® (2 ug PPS14) which elicited a titer of 776,047. Thus, optimized PCMVs containing 1.5% or 6% the amount of PPS14 contained in Prevnar® elicited a comparable anti-PPS14 antibody response. Matrivax next evaluated PCMV’s applicability to Vi antigen. SDS-PAGE data demonstrated that Vi was captured in a DNI matrix and capture ELISA further indicated that Vi antigen was localized at the surface of PCMV particles. Size fractionated Vi-DNI PMCV was compared to Typhim Vi® following a three dose, bi-weekly vaccine regimen in a murine immunogenicity study. Ten (10) ug Typhim Vi elicited an anti-Vi reciprocal antibody GMT of 200 whereas size-fractionated PCMVs containing ~2 ug Vi elicited an anti-Vi antibody GMT of \u3e600. A Vi PCMV Phase 1 clinical trial is scheduled for 2Q11

Occohannock Creek Shoreline Erosion Assessment and Living Shoreline Options Report

This study provides information to Occohannock Creek property owners to help them assess their shoreline stability and their options if erosion is a problem. In the past, shoreline erosion control options were typically limited to rip-rap, groins, or bulkheads. These hard structures often destroyed marsh and other habitat and may not have provided the protection desired. Other methods of erosion control now exist that have been used in a variety of conditions and evaluated for their durability and performance. The alternative techniques incorporate vegetation and are referred to as Living Shoreline designs. Conditions on Occohannock Creek make it a very good place to use Living Shoreline techniques to stabilize areas that are losing land or fringe marsh. All segments of Occohannock Creek can achieve some benefit by planting new marsh grasses or enhancing those already present to improve habitat, trap sediment, and reduce the erosive force of waves

The Grizzly, January 25, 2000

Bear Country Blanketed by Snow • Bigger, Better UC Beginning in the Year 2000 • Fatal Seton Hall Fire Burns in Heart of Nation • Young Boy Caught in Middle of International Custody Battle • Politician\u27s Hit-and-Run Comes Back to Haunt Him • Dickinson Librarian Imprisoned by Chinese • Collegeville Squares • The Memory of Dr. Martin Luther King Celebrated at Ursinus • Rape: What is it?? • Opinion: Russia\u27s New Year\u27s Revolution Cause for Concern?; Better Communication, Lower Prices Keys to Fixing Book-Buying Woes • Explore Careers and Gain Experience with Career Planit • Swimming Drops a Tough One to Western Maryland • Ursinus Men\u27s Basketball Atop the Centennial Conference East Division • Sports Profile: Lindsey Glah • UC Bears Defense Upsets Rosemont • Indoor Track: The Winter Warriors • Centennial Conference Coaches Attend Snell Symposium at UChttps://digitalcommons.ursinus.edu/grizzlynews/1456/thumbnail.jp

The Grizzly, February 29, 2000

Phi Psi Sanctioned • UC Students Weather Winter Sickness • Meghan Gualtieri: Profile of a True UC Role Model • Ursinus\u27 Own Superbagger • GOP Race Tightens in Michigan and Arizona • Investors to Transform Mir Into Out-of-this-World Hotel • Opinion: Food and Diversity at Ursinus College; Fox\u27s Marry a Millionaire Fiasco Sends Wrong Message • A Student\u27s proTheatre: Halves • John Gwinn: Post-Modernist Extraordinaire? • Gymnastics Sustains Record-Breaking Run at Rutgers • UC Grad Bill Stiles Becomes Sports Information Director • Winter Track Season Ends Strong • Bears Captures Last Three Wins • Sports Profile: Yori Adegunwahttps://digitalcommons.ursinus.edu/grizzlynews/1461/thumbnail.jp

The Grizzly, April 18, 2000

Celebrating Diversity: A Week of Education and Enlightenment • Questions Arise Over Accuracy of UC Student Election Results • S.T.A.R. to Shine in Sexual Assault Awareness Week • Diversity Discussion Unites \u27A Class Divided\u27 • Race Debate Heats up During Diversity Week Deliberation: Students and Faculty Dispute Affirmative Action • Profile of a Protest • Letters to the Editor • Machinal Directing Compelling • proTheatre\u27s Machinal a Masterpiece • Bears Lacrosse Squad Continues its Winning Streak • Softball Sweeps Lebanon Valley, Improves to 28-8 • Playing from the Other Side: UC Athletes Turn Coaches • Profiles: Ryan Warden; Eboni Woodard • Bears Gear Up for CC Playoffs • Golf Team Plays Up to Parhttps://digitalcommons.ursinus.edu/grizzlynews/1466/thumbnail.jp