Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70
- PMID: 39047117
- DOI: 10.1126/scitranslmed.adm8451
Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70
Erratum in
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Erratum for the Research Article "Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70" by B. Brook et al.Sci Transl Med. 2024 Sep 11;16(764):eads5741. doi: 10.1126/scitranslmed.ads5741. Epub 2024 Sep 11. Sci Transl Med. 2024. PMID: 39259814 No abstract available.
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.
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