Virology & Mycology
Open Access
ISSN: 2161-0517
ISSN: 2161-0517
Bin Lu, Hong Jin, Hui Liu, Fiona Fernandes, Weijia Wang, David Tabor, Seme Diallo, Alexey Ruzin, Qing Zhu, Mark Esser and JoAnn Suzich
MedImmune, USA
Scientific Tracks Abstracts: Virol Mycol
RSV is a leading cause of lower respiratory tract infections in infants. Palivizumab is the only approved agent for RSV prophylaxis limited to high-risk infants. MEDI8897, a potent anti-RSV F mAb with extended serum half-life, is under clinical investigation as a candidate for RSV passive vaccination in all infants entering their first RSV season. To monitor current RSV genotypes in circulation and natural polymorphisms in the F protein-binding regions of MEDI8897 and palivizumab, we determined G and F sequences of 1,228 RSV isolates collected in the OUTSMART surveillance program during 2015-16 (n=392) and 2016-17 (n=836) RSV seasons from 25 regional laboratories in the US and Puerto Rico. RSV A (62% in 2015- 16 and 45% in 2016-17), RSV B (37% in 2015-16 and 54% in 2016-17), and RSVA/RSVB coinfection (1% in both seasons) were detected. All RSV A and RSV B isolate clustered into ON1 and BA genotypes, respectively. A few distinct substitution polymorphisms in the MEDI8897 binding region (AA62-69 and 196-212) of the F protein were identified in RSV A (residues 65, 68 or 206) and RSV B (residues 66, 209, 210 and double 201/209, 206/209) strains. The frequency of these variants was in the 0.2-2.1% range, except for the 206/209 variant detected at a frequency of ~19% in 2016-17. None of these F polymorphisms had an impact on viral susceptibility to MEDI8897 neutralization. One known palivizumab resistant variant at residue 272 of RSV A was observed in the palivizumab binding region (AA267-275). The ongoing OUTSMART study provides viral susceptibility monitoring for anti-RSV mAbs.
Bin Lu, PhD is currently Principle Scientist at Medimmune/AstraZeneca. He has 18 years of preclinical and clinical experience in the development of vaccines, monoclonal antibodies for infectious diseases. His experience includes Sr Direction and VP of R&D in a biotech startup and Co-PI for the CRADA programs with NIH on the evaluation of novel vaccines and antivirals. Dr Lu has authored over twenty peer-reviewed publications and is an inventor on several US patents related to development and production of vaccines for influenza and other serious viral respiratory diseases.
E-mail: lub@medimmune.com