作者
Tom Y-H Wu, Manmohan Singh, Andrew T Miller, Ennio De Gregorio, Francesco Doro, Ugo D’Oro, David AG Skibinski, M Lamine Mbow, Simone Bufali, Ann E Herman, Alex Cortez, Yongkai Li, Bishnu P Nayak, Elaine Tritto, Christophe M Filippi, Gillis R Otten, Luis A Brito, Elisabetta Monaci, Chun Li, Susanna Aprea, Sara Valentini, Samuele Calabrό, Donatello Laera, Brunella Brunelli, Elena Caproni, Padma Malyala, Rekha G Panchal, Travis K Warren, Sina Bavari, Derek T O’Hagan, Michael P Cooke, Nicholas M Valiante
发表日期
2014/11/19
期刊
Science translational medicine
卷号
6
期号
263
页码范围
263ra160-263ra160
出版商
American Association for the Advancement of Science
简介
Adjuvants increase vaccine potency largely by activating innate immunity and promoting inflammation. Limiting the side effects of this inflammation is a major hurdle for adjuvant use in vaccines for humans. It has been difficult to improve on adjuvant safety because of a poor understanding of adjuvant mechanism and the empirical nature of adjuvant discovery and development historically. We describe new principles for the rational optimization of small-molecule immune potentiators (SMIPs) targeting Toll-like receptor 7 as adjuvants with a predicted increase in their therapeutic indices. Unlike traditional drugs, SMIP-based adjuvants need to have limited bioavailability and remain localized for optimal efficacy. These features also lead to temporally and spatially restricted inflammation that should decrease side effects. Through medicinal and formulation chemistry and extensive immunopharmacology, we show that in …
学术搜索中的文章
TYH Wu, M Singh, AT Miller, E De Gregorio, F Doro… - Science translational medicine, 2014