Controlled human infection with RSV: the opportunities of experimental challenge
File(s)
Published version
Author(s)
Habibi, MS
Chiu, C
Type
Journal Article
Abstract
Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients. Not only can they be used for early proof-of-concept clinical trials to test vaccine efficacy, but human challenge studies also offer the potential to better understand protective immunity against RSV infection to improve vaccine design and delivery. In the past, controlled human infection studies with RSV have been instrumental in elucidating the influence of factors such as route of infection and type of inoculum on the course of disease. Recently, efficacy trials of novel RSV antiviral drugs have also been successfully undertaken. Now, with advances in technology, detailed investigations of human mucosal immunity in the RSV-infected airway are possible. These have indicated defects in RSV-induced humoral and CD8+ T cell immunity that may contribute to the recurrent symptomatic infection that occurs throughout life and should be circumvented by optimal vaccines. Here, we discuss the insights derived from RSV human challenge models; the major impediments to their more widespread uptake; and their potential benefit in accelerating vaccine development, including future directions to further enhance the relevance of these models to at-risk patient populations.
Date Issued
2016-11-23
Date Acceptance
2016-11-01
Citation
Vaccine, 2016, 35 (3), pp.489-495
ISSN
1873-2518
Publisher
Elsevier
Start Page
489
End Page
495
Journal / Book Title
Vaccine
Volume
35
Issue
3
Sponsor
Medical Research Council (MRC)
Wellcome Trust
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27889256
PII: S0264-410X(16)30793-9
Grant Number
G0902266
N/A
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
RSV
Clinical trial
Antibody
T cell
RESPIRATORY SYNCYTIAL VIRUS
T-CELLS
ADULT VOLUNTEERS
IMMUNITY
MEMORY
DISEASE
VACCINATION
ILLNESS
GLYCOPROTEIN
MECHANISMS
Virology
06 Biological Sciences
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
Publication Status
Published
Coverage Spatial
Netherlands