Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70
Byron Brook, Valérie Duval, Soumik Barman, Lauren Speciner, Cali Sweitzer, Asad Khanmohammed, Manisha Menon, K. Wade Foster, Pallab Ghosh, Kimia Abedi, Jacob A. Koster, Etsuro Nanishi, Lindsey R. Baden, Ofer Levy, Thomas C. VanCott, Romain Micol, David J. Dowling
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.