IL-7 promotes mRNA vaccine-induced long-term immunity

J Nanobiotechnology. 2024 Nov 16;22(1):716. doi: 10.1186/s12951-024-02993-5.

Abstract

Messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, improving the immunogenicity and durability of mRNA vaccines remains a challenge. To elicit optimal immune responses, integrating antigen-encoded mRNA and immunostimulatory adjuvants into a single formulation is a promising approach to enhancing the efficacy of mRNA vaccines. Here, we report an adjuvant strategy to enhance the efficacy of mRNA vaccines by co-loading mRNA encoding the antigen (rabies virus glycoprotein, RABV-G) and mRNA encoding IL-7 into lipid nanoparticles, achieving co-delivery to the same antigen-presenting cells. A single immunization with G&IL-7 mRNA vaccine elicited robust humoral immune responses in mice and conferred complete protection against RABV challenge. Notably, the high levels of neutralizing antibody induced by the G&IL-7 mRNA vaccine were maintained for at least 6 months, providing mice with long-term significant and complete protection against RABV. Additionally, IL-7 also enhanced antibody responses against the SARS-CoV-2. These data demonstrate that IL-7 is a potent mRNA vaccine adjuvant that can provide the required immune stimulation in various mRNA vaccine formulations.

Keywords: Adjuvant; IL-7; Lipid nanoparticles; Long-term protection; mRNA vaccine.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Vaccine / chemistry
  • Animals
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral / immunology
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines* / immunology
  • Female
  • Humans
  • Immunity, Humoral
  • Interleukin-7* / immunology
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • RNA, Messenger / genetics
  • Rabies Vaccines / immunology
  • SARS-CoV-2 / immunology
  • mRNA Vaccines*

Substances

  • mRNA Vaccines
  • Antibodies, Neutralizing
  • Interleukin-7
  • COVID-19 Vaccines
  • Antibodies, Viral
  • Adjuvants, Immunologic
  • Rabies Vaccines
  • Lipid Nanoparticles
  • RNA, Messenger
  • Adjuvants, Vaccine
  • Liposomes