TY - JOUR
T1 - Controlled Human Infection Models To Accelerate Vaccine Development
AU - Choy, Robert K.M.
AU - Bourgeois, A. Louis
AU - Ockenhouse, Christian F.
AU - Walker, Richard I.
AU - Sheets, Rebecca L.
AU - Flores, Jorge
N1 - Funding Information:
This study was funded by a grant to PATH from the Bill & Melinda Gates Foundation (OPP1140594). The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The authors declare they have no financial conflicts of interest in any of the products described here.
Publisher Copyright:
2022 American Society for Microbiology. All Rights Reserved.
PY - 2022/9
Y1 - 2022/9
N2 - SUMMARY The timelines for developing vaccines against infectious diseases are lengthy, and often vaccines that reach the stage of large phase 3 field trials fail to provide the desired level of protective efficacy. The application of controlled human challenge models of infection and disease at the appropriate stages of development could accelerate development of candidate vaccines and, in fact, has done so successfully in some limited cases. Human challenge models could potentially be used to gather critical information on pathogenesis, inform strain selection for vaccines, explore cross-protective immunity, identify immune correlates of protection and mechanisms of protection induced by infection or evoked by candidate vaccines, guide decisions on appropriate trial endpoints, and evaluate vaccine efficacy. We prepared this report to motivate fellow scientists to exploit the potential capacity of controlled human challenge experiments to advance vaccine development. In this review, we considered available challenge models for 17 infectious diseases in the context of the public health importance of each disease, the diversity and pathogenesis of the causative organisms, the vaccine candidates under development, and each model’s capacity to evaluate them and identify correlates of protective immunity. Our broad assessment indicated that human challenge models have not yet reached their full potential to support the development of vaccines against infectious diseases. On the basis of our review, however, we believe that describing an ideal challenge model is possible, as is further developing existing and future challenge models.
AB - SUMMARY The timelines for developing vaccines against infectious diseases are lengthy, and often vaccines that reach the stage of large phase 3 field trials fail to provide the desired level of protective efficacy. The application of controlled human challenge models of infection and disease at the appropriate stages of development could accelerate development of candidate vaccines and, in fact, has done so successfully in some limited cases. Human challenge models could potentially be used to gather critical information on pathogenesis, inform strain selection for vaccines, explore cross-protective immunity, identify immune correlates of protection and mechanisms of protection induced by infection or evoked by candidate vaccines, guide decisions on appropriate trial endpoints, and evaluate vaccine efficacy. We prepared this report to motivate fellow scientists to exploit the potential capacity of controlled human challenge experiments to advance vaccine development. In this review, we considered available challenge models for 17 infectious diseases in the context of the public health importance of each disease, the diversity and pathogenesis of the causative organisms, the vaccine candidates under development, and each model’s capacity to evaluate them and identify correlates of protective immunity. Our broad assessment indicated that human challenge models have not yet reached their full potential to support the development of vaccines against infectious diseases. On the basis of our review, however, we believe that describing an ideal challenge model is possible, as is further developing existing and future challenge models.
KW - controlled human infection model
KW - human challenge model
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85138460225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138460225&partnerID=8YFLogxK
U2 - 10.1128/cmr.00008-21
DO - 10.1128/cmr.00008-21
M3 - Article
C2 - 35862754
AN - SCOPUS:85138460225
SN - 0893-8512
VL - 35
SP - 1
EP - 163
JO - Clinical Microbiology Reviews
JF - Clinical Microbiology Reviews
IS - 3
ER -