Molecular Analysis of Respiratory Syncytial Virus (RSV) F and G Proteins In the OUTSMART Surveillance Program During the 2015–2016 Winter Season in the United States

• Published in: Open forum infectious diseases Vol. 4; no. suppl_1; pp. S575 - S576
• Main Authors: Lu, Bin, Chu, Marla, Tabor, David E, Tovchigrechko, Andrey, Wang, Weijia, Fernandes, Fiona, Diallo, Seme, Ruzin, Alexey, Zhu, Qing, Jin, Hong, Esser, Mark T
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.10.2017
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofx163.1504

Abstract Background RSV is a common cause of lower respiratory tract infections. Palivizumab, a monoclonal antibody (mAb) targeting the fusion (F) protein, is the only approved agent for RSV prophylaxis, but is limited to high-risk infants. MEDI8897, a human IgG1 mAb with an extended half-life targeting the prefusion conformation of F, is being developed for prevention of RSV disease in all infants in their first RSV season. To monitor the polymorphisms in the binding regions of palivizumab and MEDI8897 in RSV F of circulating strains, we sequenced RSV isolates collected from the OUTSMART surveillance program from the 2015–16 RSV season. Methods The RSV F and G genes were RT-PCR amplified and sequenced directly from RSV positive nasal specimens. Sequence alignment and phylogenetic analyses were performed to determine viral subtypes, genotypes and amino acid (AA) variations in the F protein binding regions of MEDI8897 (AA62-69 and 196–212) and palivizumab (AA267-275). Results A total of 392 sequences were obtained and subtyped as RSV A (n = 242; 61.7%), RSV B (n = 146; 37.3%) or mixture of RSV A and RSV B (n = 4; 1.0%). Phylogenetic analysis showed that all RSV A isolates clustered into the ON1 genotype and all RSV B isolates into the BA9 genotype. Polymorphisms in the MEDI8897 binding region were identified in one RSV A isolate containing K65R and two RSV B isolates harboring Q209K and N201S/Q209K, however, none of these polymorphisms had an impact on the susceptibility to MEDI8897 neutralization. No variation was observed in the palivizumab binding site. Conclusion RSV A and B co-circulated during the 2015–16 season with RSV A strains more prevalent. The F protein residues in the binding region of MEDI8897 and palivizumab were highly conserved in these isolates. Figure 1 RSV F sequence diversity across the US geographic regions. Maximum likelihood plots of F phylogenetic tree with their relative distribution within five CDC census regions. There is only one dominant population (indicated by *) of each subtype. Figure 2 RSV F sequence diversity among age groups. Maximum likelihood plots of F phylogenetic tree for RSV A (n = 187) and RSV B (n = 127) colored by the group of a median patient age for each unique sequence. Infant, ≤1year old; senior, ≥65 years old. Circles representing the count size are for each branch. RSV F sequence is more diverse in infants. Disclosures B. Lu, Medimmune: Employee, Salary; M. Chu, MedImmune: Employee, Salary; D. E. Tabor, MedImmune: Employee, Salary; A. Tovchigrechko, MedImmune: Employee and Shareholder, Long-term incentive stock grant and Salary; W. Wang, MedImmune: Employee, Salary; F. Fernandes, MedImmune: Employee, Salary; S. Diallo, MedImmune: Employee, Salary; A. Ruzin, Medimmune: Employee and Shareholder, Salary; Q. Zhu, MedImmune: Employee, Salary; H. Jin, MedImmune: Employee, Salary; M. T. Esser, MedImmune: Employee and Shareholder, Salary