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Title: Early type I IFN blockade improves the efficacy of viral vaccines

Type I interferons (IFN-I) are a major antiviral defense and are critical for the activation of the adaptive immune system. However, early viral clearance by IFN-I could limit antigen availability, which could in turn impinge upon the priming of the adaptive immune system. In this study, we hypothesized that transient IFN-I blockade could increase antigen presentation after acute viral infection. To test this hypothesis, we infected mice with viruses coadministered with a single dose of IFN-I receptor–blocking antibody to induce a short-term blockade of the IFN-I pathway. This resulted in a transient “spike” in antigen levels, followed by rapid antigen clearance. Interestingly, short-term IFN-I blockade after coronavirus, flavivirus, rhabdovirus, or arenavirus infection induced a long-lasting enhancement of immunological memory that conferred improved protection upon subsequent reinfections. Short-term IFN-I blockade also improved the efficacy of viral vaccines. These findings demonstrate a novel mechanism by which IFN-I regulate immunological memory and provide insights for rational vaccine design.

 
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PAR ID:
10184971
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  
Publisher / Repository:
DOI PREFIX: 10.1084
Date Published:
Journal Name:
Journal of Experimental Medicine
Volume:
217
Issue:
12
ISSN:
0022-1007
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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