Type I interferon promotes humoral immunity in viral vector vaccination

Chaojie Zhong, Fengliang Liu, Renee J. Hajnik, Lei Yao, Kangjing Chen, Meirong Wang, Yuejin Liang, Jiaren Sun, Lynn Soong, Wei Hou, Haitao Hu

Research output: Contribution to journalArticlepeer-review


Recombinant viral vectors represent an important platform for vaccine delivery. Our recent studies have demonstrated distinct innate immune profiles in responding to viral vectors of different families (e.g., adenovirus versus poxvirus): while human Ad5 vector is minimally innate immune stimulatory, the poxviral vector ALVAC induces strong innate response and stimulates type I interferon (IFN) and inflammasome activation. However, the impact of the innate immune signaling on vaccine-induced adaptive immunity in viral vector vaccination is less clear. Here, we show that Modified Vaccinia Ankara (MVA), another poxviral vector, stimulated a type I IFN response in innate immune cells through cGAS-STING. Using MVA-HIV vaccine as a model, we found that type I IFN signaling promoted the generation of humoral immunity in MVA-HIV vaccination in vivo. Following vaccination, type I IFN receptor-knockout (IFNAR1-/-) mice produced significantly lower levels of total and HIV gp120-specific antibodies compared to wild-type (WT) mice. Consistent with the antibody response, a type I IFN signaling deficiency also led to reduced levels of plasma cells and memory-like B cells compared to WT mice. Furthermore, analysis of vaccine-induced CD4 T cells showed that type I IFN signaling also promoted the generation of a vaccine-specific CD4 T-cell response and a T follicular helper (Tfh) response in mice. Together, our data indicate a role for type I IFN signaling in promoting humoral immunity in poxviral vector vaccination. The study suggests that modulating type I IFN and its associated innate immune pathways will likely affect vaccine efficacy.

Original languageEnglish (US)
Article numbere00925-21
JournalJournal of virology
Issue number22
StatePublished - Nov 2021


  • HIV
  • MVA
  • Type I IFN
  • Vaccination
  • Viral vector

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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