Fc engineered anti-virus therapeutic human IgG1 expressed in plants with altered binding to the neonatal Fc receptor.

Production of therapeutic monoclonal antibody (mAb) in transgenic plants has several advantages such as large-scale production and the absence of pathogenic animal contaminants. However, mAb with high mannose (HM) type glycans has shown a faster clearance compared to antibodies produced in animal cells. The neonatal Fc receptor (FcRn) regulates the persistence of immunoglobulin G (IgG) by the FcRn-mediated recycling pathway, which salvages IgG from lysosomal degradation within cells. In this study, Fc-engineering of antirabies virus therapeutic mAb SO57 with the endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) (mAbpK SO57) in plant cell was conducted to enhance its binding activity to human neonatal Fc receptor (hFcRn), consequently improve its serum half-life. Enzyme-linked immunosorbent assay (ELISA) and Surface plasmon resonance assay showed altered binding affinity of the Fc region of three different mAbpK SO57 variants [M252Y/S254T/T256E (MST), M428L/N434S (MN), H433K/N434F (HN)] to hFcRn compared to wild type (WT) of mAbpK SO57. Molecular modeling data visualized the structural alterations in these mAbpK SO57. All of the mAbpK SO57 variants had HM type glycan structures similar to the WT mAbpK SO57. In addition, the neutralizing activity of the three variants against the rabies virus CVS-11 was effective as the WT mAbpK SO57. These results indicate that the binding affinity of mAbpK SO57 variants to hFcRn can be modified without alteration of N-glycan structure and neutralization activity. Taken together, this study suggests that Fc-engineering of antirabies virus mAb can be applied to enhance the efficacy of therapeutic mAbs in plant expression systems.

Effects of µ-Opioid Receptor Gene Polymorphism on Postoperative Nausea and Vomiting in Patients Undergoing General Anesthesia with Remifentanil: Double Blinded Randomized Trial.

Association between postoperative nausea and vomiting (PONV) and µ-opioid receptor A118G single nucleotide polymorphism (SNP) is undefined and might underlie inconsistent results of studies on PONV occurrence in patients undergoing general anesthesia with the opioid, remifentanil. Four hundred and sixteen Korean women undergoing breast surgery with general anesthesia were randomized to receive remifentanil 10 ng/mL (plasma-site, Minto model) using a target-controlled infusion device and either propofol for total intravenous anesthesia (T group) or sevoflurane for inhalation anesthesia (I group) with bispectral index values maintained between 40 and 60. Blood specimens were collected after anesthesia induction for A118G SNP analysis. PONV and postoperative pain were evaluated. A118G SNP type distribution among Korean female adults studied was AG (n=195)>AA (n=158)>GG (n=63). Regardless of anesthetic technique, patients with GG types had lower PONV scale on arrival at postoperative care unit (PACU) (P=0.002), while T group showed lower PONV scale than I group up to 6 hr after PACU discharge in AA and AG types. No differences were apparent for postoperative pain among opioid receptor polymorphism. PONV occurrence differs according to opioid receptor polymorphism and anesthetic technique in patients undergoing general anesthesia with remifentanil.

Prevalence of pediculosis capitis among Korean children.

Pediculus humanus capitis is an ectoparasite, which causes scalp pruritus particularly among children. A total of 15,373 children including 8,018 boys and 7,355 girls from 26 primary schools and 15 kindergartens attached to the primary schools and a total of 33 children from an orphanage were examined for head lice infestation (HLI). The overall prevalence of HLI in this study was 4.1% including 3.7% of the urban areas and 4.7% of the rural areas. Head lice were found more frequently in girls than in boys with prevalence of 6.5% and 1.9%, respectively. The infestation rate by school grade was 3.2%, 4.7%, 4.2%, 5.0%, 4.9%, 3.8%, and 2.1% for kindergarten, first, second, third, fourth, fifth, and sixth grades, respectively. The infestation rate of the children in an orphanage was 66.7%. The prevalence of HLI has decreased especially in the rural areas. However, HLI is a still health problem of kindergarteners and primary schoolchildren in Korea.