Academic Journal
Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis
| Title: | Forward and reverse translational approaches to predict efficacy of neutralizing respiratory syncytial virus (RSV) antibody prophylaxis |
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| Authors: | 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 |
| Source: | EBioMedicine, Vol 73, Iss , Pp 103651- (2021) |
| Publisher Information: | Elsevier, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Medicine LCC:Medicine (General) |
| Subject Terms: | Respiratory Syncytial Virus, Monoclonal Antibody, RSV, Meta-analysis, Modelling and Simulation, Human Challenge Study, Medicine, Medicine (General), R5-920 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2352-3964 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S235239642100445X; https://doaj.org/toc/2352-3964 |
| DOI: | 10.1016/j.ebiom.2021.103651 |
| Access URL: | https://doaj.org/article/29110f874edd46dea00e331b42ac8484 |
| Accession Number: | edsdoj.29110f874edd46dea00e331b42ac8484 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2021.103651 |
| Published in: | EBioMedicine |
| Language: | English |