Abstract:Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance.
“…Despite relatively rare usage of the antibody and the highly conserved nature of its viral protein target, resistance has been reported due to variations in the fusion protein binding site. [64][65][66][67][68] One study 69 investigated the human monoclonal antibody MPE8, which cross-neutralises respiratory syncytial virus and human metapneumovirus by binding to two highly conserved anti-parallel β-strands on the pre-fusion viral fusion protein. The investigators found naturally occurring antibodies with this same target specificity in some patient serum samples, and therefore proposed this pre-fusion viral fusion protein as a potential vaccine candidate.…”
Section: Antiviral Drug and Vaccine Developmentmentioning
“…Despite relatively rare usage of the antibody and the highly conserved nature of its viral protein target, resistance has been reported due to variations in the fusion protein binding site. [64][65][66][67][68] One study 69 investigated the human monoclonal antibody MPE8, which cross-neutralises respiratory syncytial virus and human metapneumovirus by binding to two highly conserved anti-parallel β-strands on the pre-fusion viral fusion protein. The investigators found naturally occurring antibodies with this same target specificity in some patient serum samples, and therefore proposed this pre-fusion viral fusion protein as a potential vaccine candidate.…”
Section: Antiviral Drug and Vaccine Developmentmentioning
“…While the impact that widespread use of anti-RSV F MAbs will have on the emergence and transmission of resistant variants is unknown, these variants may also arise naturally in the absence of drug selection pressure. To date, palivizumab resistance-associated polymorphisms have been rarely observed in circulating RSV strains ( 35 ). Consistent with these reports, the restricted use of palivizumab (Synagis) ( 7 ), and the growth disadvantage of resistant variants in the absence of palivizumab selective pressure ( 36 ), we observed no known palivizumab target site II polymorphisms among 2017–2018 RSV strains.…”
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. INFORM-RSV is a multi-year clinical study designed to describe the global molecular epidemiology of RSV in children under five years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. During the pilot season (2017–2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, the Netherlands, Finland, Japan, Brazil, South Africa, and Australia). RSV B (all BA9 genotype) predominated over RSV A (all ON1 genotype) globally (69.0% vs. 31.0%) and in all countries except South Africa. Geographic clustering patterns highlighted wide transmission and continued evolution with viral spread. Most RSV were from infants <1 year of age (81.2%), males (56.3%), and patients hospitalized >24 hours (70.5%) with no differences in subtype distribution. Compared to 2013 reference sequences, variations at F protein antigenic sites were observed for both RSV A and B strains with high frequency polymorphisms at antigenic site Ø (I206M/Q209R) and site V (L172Q/S173L/K191R) in RSV B strains. The INFORM-RSV 2017–2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and mAbs under development.
Antigenic and genetic characteristics of Russian RSV isolates are presented for the first time. Of the 69 strains isolated in St. Petersburg, 93% belonged to the RSV-A antigenic group. The antigenic variations in the F-protein RSV were analyzed using a panel from 6 monoclonal antibodies by the method of micro-cultural ELISA. Depending on the decrease in the effectiveness of interaction with monoclonal antibodies (relative to the reference strain Long), RSV-A isolates were divided into 4 antigenic subgroups. The results of 24 isolates sequencing showed that more than 60% of them had substitutions in significant F-protein sites compared to the ON67-1210A reference strain of the current RSV genotype ON1/GA2. The most variable were the signal peptide and antigenic site II. When comparing the results of ELISA and sequencing, it was not possible to identify any specific key substitutions in the amino acid sequence of the F-protein that affect the interaction of the virus with antibodies. The nucleotide sequence of the F-gene from 19 of the 24 characterized isolates was close to that of ON67-1210A reference virus and was significantly different from RSV-A Long and A2 viruses. A separate group consisted of 5 strains, in which the F-protein structure was approximated to RSV Long.
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