• Journal of Microbiology and Biotechnology
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• 제13권3호
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• pp.469-472
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• 2003

A method that effectively precipitates capsular polysaccharide of Haemophilus influenzae type b (polyribosylribitol phosphate, PRP) conjugated to tetanus toxoid (TT), PRP TT in a liquid vaccine has been developed to measure free PRP present in TT-conjugate vaccine. The method involves adding anti-TT antibody and ammonium sulfate to precipitate PRP-TT conjugate and measuring free PRP in tile supernatant. This new method provides a complete precipitation of the total PRP-TT, and provides an accurate and reproducible measurements of free PRP. The accuracy of the assay was confirmed by spiking known amounts of unconjugated PRP to PRP-TT conjugate, and the new method was found to have no effect on free PRP while precipitating PRP-TT. The published acid precipitation method did not produce reproducible results due to incomplete precipitation of PRP-TT, especially when the vaccine is formulated in a salt-buffered solution.

• Clinical and Experimental Pediatrics
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• 제54권4호
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• pp.146-151
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• 2011

Streptococcus pneumoniae remains a leading cause of invasive infections including bacteremia and meningitis, as well as mucosal infections such as otitis media and pneumonia among children and adults. The 7-valent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease (IPD) by the vaccine serotypes among the vaccinees and substantial declines in IPD among unvaccinated populations such as older children and adults as well. In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of IPD, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is an increase in the number of IPDs caused by nonvaccine serotypes, though it is much smaller than overall declines of vaccine serotype diseases. Several vaccines containing additional serotypes have been developed and tested clinically in order to expand the range of serotypes of Streptococcus pneumoniae. Recently two new pneumococcal protein conjugate vaccines, 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13), have been approved for use in several countries including Korea. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society.

• Clinical and Experimental Pediatrics
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• 제49권3호
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• pp.242-250
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• 2006

Haemophilus influenzae type b(Hib) conjugate vaccines prevent Hib disease in individuals and reduce the carriage and transmission of the organism in the community. The incidence of Hib disease has been decreased dramatically in a diverse range of countries through the use of a variety of conjugate vaccines and vaccine schedules. In some countries, the vaccine has caused a near-disappearance of invasive Hib disease through a combination of direct protection and herd immunity. The effectiveness of the vaccine was not modified by the type of conjugate vaccine, the number of doses given(two, three or four), age at first vaccination(two months, 42 to 90 days, three months) and whether the vaccine was tested in an industrialized or developing country. Over 15 years of international experience with vaccines has also demonstrated that they are safe. In 2004, Hib vaccines were adapted in routine immunization in 92 countries in the world. Decisions regarding the use of the Hib vaccine in routine immunization schedules depend not only on the effectiveness and efficacy of the vaccine but also on factors such as burden of disease, vaccine cost, and competing priorities. In Korea, Hib disease burden seemed to be lower than other developed countries(~10/100,000). Moreover Hib vaccines showed excellent immunogenicity in Korean children in many studies. Therefore, a potential approach to economize the cost of Hib vaccines could be to explore the possibilities of using reduced vaccine doses for immunization as some other countries.

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권6호
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• pp.490-494
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• 2004

An efficacy test of PRP (polyribosylribitol phosphate)-TT (Tetanus toxoid) conjugate vaccines was carried out using BALB/c mice as an animal model by inoculating Haemophilus in­fluenzae type b (Hib) with a virulence enhancement factor (VEF). Three administrations of the conjugate vaccines at 2-week intervals elicited a significantly high level of PRP antibodies (P>0.0001). The protective activity of the PRP immunization was challenged with either Hib with iron dextran (Hib/) or with a combination of mucin and hemoglobin (Hibmh) as a VEF. The me­dium lethal dose $(LD_{50})$ for Hibmh and Hibiwas measured as 10 CFU (Colony Forming Unit) and $2.5{\times}10^{8}$ CFU respectively. Each immunized animal was challenged with five or ten times the $LD_{50}$ level of bacteria with a VEF. A significant difference in mortality between the immunized and control mice (P> 0.01) was observed with the Hibmh challenge inoculation but not with the Hibi challenge inoculation. These results show that a combination of mucin and hemoglobin was able to enhance the virulence of Hib in BALB/c mice to cause a lethal infection, thus suggesting that BALB/c mice introduced to this method can be an effective model animal for testing the protective efficacy of H. influenzae conjugate vaccines.

• Biotechnology and Bioprocess Engineering:BBE
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• 제11권3호
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• pp.215-222
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• 2006

The Lowry method was used in this study to measure protein in Haemophilus influenzae type b (Hib) conjugate vaccines (polyribosylibitol phosphate-tetanus toxoid; PRP-TT) using deoxycholic acid (DOC) to induce protein precipitation. Trichloroacetic acid (TCA) did not induce precipitation adequately from the Hib conjugate bulk and the freeze-dried Hib conjugate product. Its yield was approximately 50%. The matrix structure of Hib conjugate inhibits precipitation by TCA. Although the Lowry method can be carried out without precipitation in Hib conjugate bulk when no residual impurities (adipic acid dihydrazide [ADH], 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide-HCI [EDAC], phenol and cyanogens bromide [CNBr], etc.) are present, it cannot be used for Hib conjugate products that contain sucrose 8.5%, because 8.5% concentration of sucrose enhanced the protein concentration. DOC- and HCl-induced precipitation is an alternative method for evaluating the protein content of the Hib conjugate bulk and the Hib conjugate product. The precipitation was optimal with a final concentrate of 0.1% for DOC at $4^{\circ}C$ and pH 2. This Lowry method, using DOC/HCI precipitation to induce protein precipitation, was confirmed a consistent, reproducible, and valid test for proteins in Hib conjugate bulk and its freeze-dried product.

• Clinical and Experimental Pediatrics
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• 제57권2호
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• pp.55-66
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• 2014

The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be highly efficacious against invasive pneumococcal diseases and effective against pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in major changes in the epidemiology of pneumococcal diseases. However, pneumococcal vaccines induce serotype-specific immunity, and a relative increase in non-vaccine serotypes has been reported following the widespread use of PCV7, leading to a need for extended serotype coverage for protection. PCV10 and PCV13 have been licensed on the basis of noninferiority of immunogenicity compared to a licensed conjugate vaccine. In this article, we aimed to review important data regarding the efficacy and effectiveness of the extended-coverage PCVs published or reported thus far and to discuss future implications for pneumococcal vaccines in Korea. After the introduction of PCV10 and PCV13, within a short period of time, evidence of protection conferred by these vaccines against invasive and mucosal infections caused by most of the serotypes included in the vaccines is accumulating. The choice of vaccine should be based on the changes in the dynamics of pneumococcal serotype distribution and diseases in the region where the vaccines are to be used. Continuous surveillance is essential for the appropriate use of pneumococcal vaccines and evaluation of the impact of PCVs on pneumococcal diseases.

• Infection and chemotherapy
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• 제50권4호
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• pp.287-300
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• 2018

Pneumonia is the leading cause of morbidity and mortality, particularly in old adults. The incidence and etiologic distribution of community-acquired pneumonia is variable both geographically and temporally, and epidemiology might evolve with the change of population characteristics and vaccine uptake rates. With the increasing prevalence of chronic medical conditions, a wide spectrum of healthcare-associated pneumonia could also affect the epidemiology of community-acquired pneumonia. Here, we provide an overview of the epidemiological changes associated with community-acquired pneumonia over the decades since pneumococcal conjugate vaccine introduction.

• Clinical and Experimental Pediatrics
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• 제49권3호
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• pp.235-241
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• 2006

Streptococus pneumoniae is an important cause of invasive infections as well as non-invasive infections such as acute otitis media and sinusitis both in children and adults. Resistance of S. pneumoniae to multiple antimicrobials is increasing and poses therapeutic challenges, and prevention became more important. 23-valent polysaccharide vaccine has been used for the last several decades, but is not effective in children <2 years of age, the highest risk group of invasive diseases. Recently, a 7-valent pneumococcal protein conjugate vaccine(PCV) which is effective in infants and young children has been developed. The efficacy of PCVs against invasive pneumococcal disease and pneumonia is well established and is documented in several well-conducted studies. However, the effect of PCVs on otitis media is less obvious and more complex. PCVs clearly reduce diseases caused by vaccine-type(VT) pneumococci, but replacement of VT serotypes by non-VT serotypes in nasopharyngeal carriage of S. pneumoniae is responsible for the increase in acute otitis media caused by non-VT serotypes. Three years after introduction of PCV in the US, some increase of invasive infections with serotype 19A possibly due to serotype switching within certain vaccine type strains has been noted. Since most antibiotic-resistance in S. pneumoniae is confined to VT serotypes, vaccine use also reduces antibiotic resistance. With development of PCV, there was a great advance in the prevention of pneumococcal diseases, but replacement with potential virulent organisms and development of antibiotic resistance in non-VT pneumococci is a possibility that needs careful monitoring.

• Pediatric Infection and Vaccine
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• 제15권1호
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• pp.1-4
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• 2008

Immunizations are among the most cost-effective and widely used public health interventions. This is a report a revision of recommendation of immunization for children by Korean Pediatric Society. Immunization. Vaccines were divided into 4 groups. 1) Vaccines that are recommended to all infants and children (BCG, hepatitis B vaccine, DTaP, Td, Polio vaccine, Japanese encephalitis vaccine, MMR, varicella vaccine, influenza vaccine [6-23 months of age], H. influenzae type b vaccine), 2) those that can be administered to all infants and children, but decision of administration is made by parents (pneumococcal conjugate vaccine, hepatitis A vaccine, influenza vaccine [healthy children ${\geq}24$ months of age], rotavirus vaccine, human papilloma virus vaccine), 3) those that should be given to high risk group (pneumococcal polysaccharide vaccine [high risk patients ${\geq}24$ months of age], influenza vaccine [high risk patients ${\geq}24$ months of age], typhoid vaccine), and 4) those administered for control of outbreaks or prevention of emerging infectious diseases. Immunization schedule recommended by Korean Pediatric Society in 2008 is presented.

• Infection and chemotherapy
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• 제50권4호
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• pp.328-339
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• 2018

Background: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009-2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). Materials and Methods: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ${\geq}2$ non-${\beta}$-lactam antimicrobials. Results: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. Conclusion: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.