Virus-derived immunostimulatory RNA induces type I IFN-dependent antibodies and T-cell responses during vaccination

Vaccine. 2018 Jun 27;36(28):4039-4045. doi: 10.1016/j.vaccine.2018.05.100. Epub 2018 May 31.

Abstract

Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus. We show that DDO induces robust IgG2c antibody production when used in an inactivated influenza A virus (IAV) vaccine. Additionally, DDO induces Th1 and CD8+ T-cell responses able to protect against heterosubtypic IAV challenge. Interestingly, DDO synergized with AddaVax and skewed the immune response towards type-1 immunity. The adjuvancy of DDO alone and in synergy with AddaVax was heavily dependent on type I interferon signaling. Our data support a critical role for type I interferon in the induction of type-1 immune responses during vaccination and demonstrate that DDO is a type-1 immunity orienting vaccine adjuvant that can be used alone or in synergy with other adjuvants.

Keywords: Adjuvant; Defective viral genomes; Influenza vaccine; Type-1 immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / isolation & purification
  • Animals
  • Antibodies, Viral / blood*
  • Disease Models, Animal
  • Female
  • Influenza A virus / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Interferon Type I / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • RNA, Viral / administration & dosage*
  • RNA, Viral / isolation & purification
  • Sendai virus / chemistry*
  • T-Lymphocytes / immunology*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines
  • Interferon Type I
  • RNA, Viral
  • Vaccines, Inactivated