Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis

Background: Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neu...

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Autores principales:	Brian M. Maas, Jos Lommerse, Nele Plock, Radha A. Railkar, S.Y. Amy Cheung, Luzelena Caro, Jingxian Chen, Wen Liu, Ying Zhang, Qinlei Huang, Wei Gao, Li Qin, Jie Meng, Han Witjes, Emilie Schindler, Benjamin Guiastrennec, Francesco Bellanti, Daniel S. Spellman, Brad Roadcap, Mariya Kalinova, Juin Fok-Seang, Andrew P. Catchpole, Amy S. Espeseth, S. Aubrey Stoch, Eseng Lai, Kalpit A. Vora, Antonios O. Aliprantis, Jeffrey R. Sachs
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Respiratory Syncytial Virus Monoclonal Antibody RSV, Meta-analysis Modelling and Simulation Human Challenge Study Medicine R Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/29110f874edd46dea00e331b42ac8484
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spelling	oai:doaj.org-article:29110f874edd46dea00e331b42ac84842021-11-12T04:40:31ZForward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis2352-396410.1016/j.ebiom.2021.103651https://doaj.org/article/29110f874edd46dea00e331b42ac84842021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S235239642100445Xhttps://doaj.org/toc/2352-3964Background: Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neutralizing antibodies across patient populations exposed to a time-varying force of infection (i.e., seasonal variation) are necessary. Methods: Five decades of clinical trial literature were leveraged to build a model-based meta-analysis (MBMA) describing the relationship between RSV serum neutralizing activity (SNA) and clinical endpoints. The MBMA was validated by backward translation to animal challenge experiments and forward translation to predict results of a recent RSV mAb trial. MBMA predictions were evaluated against a human trial of 70 participants who received either placebo or one of four dose-levels of MK-1654 and were challenged with RSV [NCT04086472]. The MBMA was used to perform clinical trial simulations and predict efficacy of MK-1654 in the infant target population. Findings: The MBMA established a quantitative relationship between RSV SNA and clinical endpoints. This relationship was quantitatively consistent with animal model challenge experiments and results of a recently published clinical trial. Additionally, SNA elicited by increasing doses of MK-1654 in humans reduced RSV symptomatic infection rates with a quantitative relationship that approximated the MBMA. The MBMA indicated a high probability that a single dose of ≥ 75 mg of MK-1654 will result in prophylactic efficacy (> 75% for 5 months) in infants. Interpretation: An MBMA approach can predict efficacy of neutralizing antibodies against RSV and potentially other respiratory pathogens.Brian M. MaasJos LommerseNele PlockRadha A. RailkarS.Y. Amy CheungLuzelena CaroJingxian ChenWen LiuYing ZhangQinlei HuangWei GaoLi QinJie MengHan WitjesEmilie SchindlerBenjamin GuiastrennecFrancesco BellantiDaniel S. SpellmanBrad RoadcapMariya KalinovaJuin Fok-SeangAndrew P. CatchpoleAmy S. EspesethS. Aubrey StochEseng LaiKalpit A. VoraAntonios O. AliprantisJeffrey R. SachsElsevierarticleRespiratory Syncytial VirusMonoclonal AntibodyRSV, Meta-analysisModelling and SimulationHuman Challenge StudyMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 73, Iss , Pp 103651- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Respiratory Syncytial Virus Monoclonal Antibody RSV, Meta-analysis Modelling and Simulation Human Challenge Study Medicine R Medicine (General) R5-920
spellingShingle	Respiratory Syncytial Virus Monoclonal Antibody RSV, Meta-analysis Modelling and Simulation Human Challenge Study Medicine R Medicine (General) R5-920 Brian M. Maas Jos Lommerse Nele Plock Radha A. Railkar S.Y. Amy Cheung Luzelena Caro Jingxian Chen Wen Liu Ying Zhang Qinlei Huang Wei Gao Li Qin Jie Meng Han Witjes Emilie Schindler Benjamin Guiastrennec Francesco Bellanti Daniel S. Spellman Brad Roadcap Mariya Kalinova Juin Fok-Seang Andrew P. Catchpole Amy S. Espeseth S. Aubrey Stoch Eseng Lai Kalpit A. Vora Antonios O. Aliprantis Jeffrey R. Sachs Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
description	Background: Neutralizing mAbs can prevent communicable viral diseases. MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) under development to prevent RSV infection in infants. Development and validation of methods to predict efficacious doses of neutralizing antibodies across patient populations exposed to a time-varying force of infection (i.e., seasonal variation) are necessary. Methods: Five decades of clinical trial literature were leveraged to build a model-based meta-analysis (MBMA) describing the relationship between RSV serum neutralizing activity (SNA) and clinical endpoints. The MBMA was validated by backward translation to animal challenge experiments and forward translation to predict results of a recent RSV mAb trial. MBMA predictions were evaluated against a human trial of 70 participants who received either placebo or one of four dose-levels of MK-1654 and were challenged with RSV [NCT04086472]. The MBMA was used to perform clinical trial simulations and predict efficacy of MK-1654 in the infant target population. Findings: The MBMA established a quantitative relationship between RSV SNA and clinical endpoints. This relationship was quantitatively consistent with animal model challenge experiments and results of a recently published clinical trial. Additionally, SNA elicited by increasing doses of MK-1654 in humans reduced RSV symptomatic infection rates with a quantitative relationship that approximated the MBMA. The MBMA indicated a high probability that a single dose of ≥ 75 mg of MK-1654 will result in prophylactic efficacy (> 75% for 5 months) in infants. Interpretation: An MBMA approach can predict efficacy of neutralizing antibodies against RSV and potentially other respiratory pathogens.
format	article
author	Brian M. Maas Jos Lommerse Nele Plock Radha A. Railkar S.Y. Amy Cheung Luzelena Caro Jingxian Chen Wen Liu Ying Zhang Qinlei Huang Wei Gao Li Qin Jie Meng Han Witjes Emilie Schindler Benjamin Guiastrennec Francesco Bellanti Daniel S. Spellman Brad Roadcap Mariya Kalinova Juin Fok-Seang Andrew P. Catchpole Amy S. Espeseth S. Aubrey Stoch Eseng Lai Kalpit A. Vora Antonios O. Aliprantis Jeffrey R. Sachs
author_facet	Brian M. Maas Jos Lommerse Nele Plock Radha A. Railkar S.Y. Amy Cheung Luzelena Caro Jingxian Chen Wen Liu Ying Zhang Qinlei Huang Wei Gao Li Qin Jie Meng Han Witjes Emilie Schindler Benjamin Guiastrennec Francesco Bellanti Daniel S. Spellman Brad Roadcap Mariya Kalinova Juin Fok-Seang Andrew P. Catchpole Amy S. Espeseth S. Aubrey Stoch Eseng Lai Kalpit A. Vora Antonios O. Aliprantis Jeffrey R. Sachs
author_sort	Brian M. Maas
title	Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
title_short	Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
title_full	Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
title_fullStr	Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
title_full_unstemmed	Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
title_sort	forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (rsv) antibody prophylaxis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/29110f874edd46dea00e331b42ac8484
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Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis

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