Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70

Sci Transl Med. 2024 Jul 24;16(757):eadm8451. doi: 10.1126/scitranslmed.adm8451. Epub 2024 Jul 24.

Abstract

Messenger RNA (mRNA) vaccines were pivotal in reducing severe acute respiratory syndrome 2 (SARS-CoV-2) infection burden, yet they have not demonstrated robust durability, especially in older adults. Here, we describe a molecular adjuvant comprising a lipid nanoparticle (LNP)-encapsulated mRNA encoding interleukin-12p70 (IL-12p70). The bioactive adjuvant was engineered with a multiorgan protection (MOP) sequence to restrict transcript expression to the intramuscular injection site. Admixing IL-12-MOP (CTX-1796) with the BNT162b2 SARS-CoV-2 vaccine increased spike protein-specific immune responses in mice. Specifically, the benefits of IL-12-MOP adjuvantation included amplified humoral and cellular immunity and increased immune durability for 1 year after vaccination in mice. An additional benefit included the restoration of immunity in aged mice to amounts comparable to those achieved in young adult animals, alongside amplification with a single immunization. Associated enhanced dendritic cell and germinal center responses were observed. Together, these data demonstrate that an LNP-encapsulated IL-12-MOP mRNA-encoded adjuvant can amplify immunogenicity independent of age, demonstrating translational potential to benefit vulnerable populations.

MeSH terms

  • Adjuvants, Immunologic*
  • Adjuvants, Vaccine
  • Animals
  • BNT162 Vaccine
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines* / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Female
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Interleukin-12* / metabolism
  • Lipids / chemistry
  • Liposomes
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • mRNA Vaccines*

Substances

  • Interleukin-12
  • mRNA Vaccines
  • RNA, Messenger
  • Adjuvants, Immunologic
  • COVID-19 Vaccines
  • Lipid Nanoparticles
  • BNT162 Vaccine
  • Spike Glycoprotein, Coronavirus
  • Adjuvants, Vaccine
  • Lipids
  • spike protein, SARS-CoV-2
  • Liposomes