Prevalence and Genetic Structures of Streptococcus pneumoniae Serotype 6D, South Korea

To determine prevalence and genetic structures of new serotype 6D strains of pneumococci, we examined isolates from diverse clinical specimens in South Korea during 1991–2008. Fourteen serotype 6D strains accounted for 10.4% of serogroup 6 pneumococci from blood, sputum, nasopharynx, and throat samples. Serotype 6D strains consisted of 3 sequence types

Safety and Immunogenicity of a New Trivalent Inactivated Split-virus Influenza Vaccine in Healthy Korean Children: A Randomized, Double-blinded, Active-controlled, Phase III Study

We report results of a randomized, double-blinded, active-controlled, phase III study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (GC501) manufactured by the Green Cross Corporation in Korea. A total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either GC501 or control. Of the GC501 recipients, seroconversion occurred in 48.5% for A/H1N1, 67.7% for A/H3N2 and 52% for influenza B. The proportion of subjects who had post-vaccination hemagglutination-inhibition titers of 1:40 or greater was 90.7% for A/H1N1, 86.8% for A/H3N2 and 82.4% for influenza B in the GC501 recipients. No serious adverse events related to vaccination, or withdrawals because of adverse events were reported. The majority of solicited adverse events were mild in intensity. GC501 vaccine has good tolerability and favorable immunogenicity in children aged 6 months to < 18 yr. The addition of one more brand of influenza vaccine may allow for better global accessibility of vaccine for epidemics or future pandemics

Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases.

Transcription factor IIH (TFIIH) is a protein assembly essential for transcription initiation and nucleotide excision repair (NER). Yet, understanding of the conformational switching underpinning these diverse TFIIH functions remains fragmentary. TFIIH mechanisms critically depend on two translocase subunits, XPB and XPD. To unravel their functions and regulation, we build cryo-EM based TFIIH models in transcription- and NER-competent states. Using simulations and graph-theoretical analysis methods, we reveal TFIIHs global motions, define TFIIH partitioning into dynamic communities and show how TFIIH reshapes itself and self-regulates depending on functional context. Our study uncovers an internal regulatory mechanism that switches XPB and XPD activities making them mutually exclusive between NER and transcription initiation. By sequentially coordinating the XPB and XPD DNA-unwinding activities, the switch ensures precise DNA incision in NER. Mapping TFIIH disease mutations onto network models reveals clustering into distinct mechanistic classes, affecting translocase functions, protein interactions and interface dynamics

Safety and immunogenicity of an inactivated split-virus influenza A/H1N1 vaccine in healthy children from 6 months to < 18 years of age: A prospective, open-label, multi-center trial

This study was conducted to determine the immunogenicity and safety of an inactivated split-virus influenza A/H1N1 vaccine in healthy Korean children from 6 months to <18 years of age. The immunization schedule consisted of two vaccinations, 21 days apart. The unadjuvanted vaccine contained 7.5 mu g (subjects 6 months to <3 years of age) or 15 mu g (subjects 3 to <18 years of age) of hemagglutinin antigen per dose. A total of 251 subjects were enrolled and 248 and 242 subjects, respectively, were included in the post-first dose and post-second dose immunogenicity evaluations conducted on a per protocol basis. By day 21, after the first dose, hemagglutination-inhibition titers of 1:40 or more were observed in 5.9% of subjects 6 months to <3 years of age, 34.9% of subjects 3 to <9 years of age and 81.4% of subjects 9-18 years of age. By day 21 after the second dose, the titer had been achieved 55.9%, 69.5% and 90.5%, respectively. No vaccination-related serious adverse events were observed. A single 15-mu g dose of vaccine was highly immunogenic in subjects equal to or more than 9 years of age. However, a two-dose regimen is needed to produce potentially protective antibody titers in younger children. (C) 2010 Elsevier Ltd. All rights reserved.Nolan T, 2010, JAMA-J AM MED ASSOC, V303, P37, DOI 10.1001/jama.2009.1911Plennevaux E, 2010, LANCET, V375, P41, DOI 10.1016/S0140-6736(09)62026-2Liang XF, 2010, LANCET, V375, P56, DOI 10.1016/S0140-6736(09)62003-1JHUNG M, 2010, MMWR-MORBID MORTAL W, V59, P423Zhu FC, 2009, NEW ENGL J MED, V361, P2414, DOI 10.1056/NEJMoa0908535Greenberg ME, 2009, NEW ENGL J MED, V361, P2405, DOI 10.1056/NEJMoa0907413Hancock K, 2009, NEW ENGL J MED, V361, P1945, DOI 10.1056/NEJMoa0906453Dawood FS, 2009, NEW ENGL J MED, V360, P2605, DOI 10.1056/NEJMoa0903810FIORE AE, 2009, MMWR-MORBID MORTAL S, V58, P1*WHO, 2009, WKLY EPIDEMIOL REC, V84, P249*WHO, 2009, PAND H1N1 2009 UPD 1*CDCP, 2009, MMWR-MORBID MORTAL W, V58, P1100*VACC REL BIOL PRO, 2009, REG CONS REG US NOV, P11601*NAT I ALL INF DIS, 2009, YOUNG CHILDR 2 DOS 2*CDCP, 2009, ESET 209 H1N1 INFL C*KOR CTR DIS CONTR, 2009, SURV DAT WEEK 52, P52Talbot HK, 2008, VACCINE, V26, P4057, DOI 10.1016/j.vaccine.2008.05.024*US FDA, 2007, GUID IND CLIN DAT NE*US FDA, 2007, GUID IND TOX GRAD SCNeuzil KM, 2006, J INFECT DIS, V194, P1032Ferguson NM, 2006, NATURE, V442, P448, DOI 10.1038/nature04795ENGLUND JA, 2006, PEDIATRICS, V118, P579Hannoun C, 2004, VIRUS RES, V103, P133, DOI 10.1016/j.virusres.2004.02.025Ruben FL, 2004, CLIN INFECT DIS, V38, P678Neuzil KM, 2001, PEDIATR INFECT DIS J, V20, P733*COMM PROP MED PRO, 1997, CPMPBWP21496 EUR AGKENDAL AP, 1982, CONC PROC LAB BAS INPARKMAN PD, 1977, J INFECT DIS, V136, pS722FOY HM, 1976, J INFECT DIS, V134, P3621

A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding showed XPG acts by switching ssDNA translocation to dsDNA unwinding as a likely committed step. Pertinent to the NER pathway regulation, XPG incision activity is suppressed during coreTFIIH translocation on DNA but is licensed when coreTFIIH stalls at the lesion or when ATP hydrolysis is blocked. Moreover, ≥15 nucleotides of 5'-ssDNA is a prerequisite for efficient translocation and incision. Our results unveil a paired coordination mechanism in which key lesion scanning and DNA incision steps are sequentially coordinated, and damaged patch removal is only licensed after generation of ≥15 nucleotides of 5'-ssDNA, ensuring the correct ssDNA bubble size before cleavage

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults

Objectives: This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. Methods: Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Results: Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N = 297) or a saline placebo (N = 153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Conclusions: Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination