Early type I IFN blockade improves the efficacy of viral vaccines

Nicole Palacio, Tanushree Dangi, Young Rock Chung, Yidan Wang, Juan Luis Loredo-Varela, Zhongyao Zhang, Pablo Penaloza-MacMaster*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number20191220
JournalJournal of Experimental Medicine
Volume217
Issue number12
DOIs
StatePublished - Dec 7 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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