scholarly journals Development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains ofStreptococcus pneumoniae

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2737 ◽  
Author(s):  
Rehab H. Bahy ◽  
Hayam M. Hamouda ◽  
Amal S. Shahat ◽  
Aymen S. Yassin ◽  
Magdy A. Amin

Streptococcus pneumoniaeis a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. Protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. Pneumococcal conjugate vaccine consists of sugars (polysaccharides) from the capsule of the bacteriumS. pneumoniaethat are conjugated to a carrier protein. Three pneumococcal conjugated vaccines, each directed against a group of serotypes, are registered in Egypt; however, local vaccine production is required to cover the most prevalent serotypes. In this work, capsular polysaccharide from the most current and prevalent serotypes in Egypt were extracted, purified and conjugated to bovine serum albumin (BSA). The polysaccharide protein conjugate was purified through ultrafiltration technique and molecular size distribution was compared to an available vaccine. The immunogenicity of the prepared vaccine was examined via two methods: First, by measuring the levels of the elicited antibodies in the sera of the vaccinated mice; Second, by challenging the vaccinated groups of mice with approximately 107CFU of each specific serotype and determining the degree of protection the developled vaccine offers. Our results show that the developed conjugated capsular polysaccharide vaccine is highly immunogenic and protective in mice. This finding illustrates the importance of tracking the most recent and predominant peneumococcal serotypes to generate effective vaccines, instead of using expensive imported vaccines with large number of serotypes which might not be even present in the community.

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S367-S367
Author(s):  
Lynn-Yao Lin ◽  
McClain Vail ◽  
Dmitri Debabov ◽  
Ian Critchley

Abstract Background Ceftazidime-avibactam (CAZ-AVI) and ceftolozane-tazobactam (TOL-TAZ) are cephalosporin/β-lactamase inhibitor combinations recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). Both agents are reported to have antibacterial activity against P. aeruginosa including multi-drug-resistant strains, but few studies have directly compared the activities of both agents against the same strains in a single study. This study evaluated the activities of both agents against characterized β-lactamase-producing P. aeruginosa using broth microdilution (BMD) and disk diffusion (DD) methods. Methods A total of 98 clinical isolates of P. aeruginosa, including characterized β-lactamase-producing strains were tested for susceptibility to CAZ-AVI and TOL-TAZ using BMD and DD and results were interpreted using FDA/CLSI breakpoints. The isolates tested included CTX-M (ESBL), AmpC, KPC, OXA and metallo-β-lactamase (MBL) producing organisms. The results from both BMD and DD were analyzed to assess the correlation between the testing methods and ability to differentiate isolates susceptible and resistant to both agents. Results CAZ-AVI and TOL-TAZ exhibited similar MIC values against all isolates with MIC50/90 values of 2 and 16 µg/mL, respectively. When results were interpreted using FDA/CLSI breakpoints, the susceptibility rates for CAZ-AVI and TOL-TAZ were 82.7% and 62.2%, respectively. Isolates resistant to CAZ-AVI were predominantly MBL-producers whereas isolates resistant to TOL-TAZ included both MBL and KPC-producing P. aeruginosa. Both agents were active against AmpC-producing P. aeruginosa and both agents showed good correlation between BMD and DD methods. Conclusion CAZ-AVI and TOL-TAZ were active against β-lactamase-producing subsets of P. aeruginosa isolates in this challenge set. Both AmpC and KPC-producing P. aeruginosa were susceptible to CAZ-AVI whereas TOL-TAZ activity was limited to AmpC-producing organisms. Neither agent was active against MBL-producing organisms. Disclosures L. Y. Lin, Allergan plc: Employee, Salary; M. Vail, Allergan plc: Employee and Intern during study conduct and analysis, Educational support; D. Debabov, Allergan plc: Employee, Salary; I. Critchley, Allergan plc: Employee, Salary


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