Low resistance against a novel highly potent site IV antibody

Tang A, Chen Z, Cox KS, Su HP, Callahan C, Fridman A, Zhang L, Patel SB, Cejas PJ, Swoyer R, Touch S, Citron MP, Govindarajan D, Luo B, Eddins M, Reid JC, Soisson SM, Galli J, Wang D, Wen Z, Heidecker GW, Casimiro DR, DiStefano DJ & Vora KA.

RB1 is a human monoclonal antibody that binds to site IV of the RSV F glycoprotein and is 50 times more potent than palivizumab. Tang and colleagues describe the crystal structure of RB1 and how it recognizes both RSV preF and RSV postF. They show that natural resistance occurs in less than one percent of more than 3000 isolates available in GenBank. The authors also demonstrate excellent neutralization of clinical isolates. RB1 is different from MEDI8897 because it binds to another site of RSV F, it recognized both preF and postF and appears to have a lower frequency of natural resistant clinical isolates. MK-1654 is an extended half-life version of RB1 (half-life 70-85 days) by introduction of a YTE mutation of the Fc part of the antibody. Merck is aims to develop MK-1654 for use in preterm as well as term children. The results of a phase 1-2 trial are expected in 2022 (www.clinicaltrials.gov). This paper shows that MK-1654 as the potential to be developed as a universal RSV passive immunization solution.

Download | Paper of the Month October 2019