tetano
Editor, Senior Moderator
Sci Transl Med
. 2024 Jul 24;16(757):eadm8451.
doi: 10.1126/scitranslmed.adm8451. Epub 2024 Jul 24. Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70
Byron Brook[SUP] 1 2 [/SUP], Valerie Duval[SUP] 3 [/SUP], Soumik Barman[SUP] 1 2 [/SUP], Lauren Speciner[SUP] 3 [/SUP], Cali Sweitzer[SUP] 1 [/SUP], Asad Khanmohammed[SUP] 3 [/SUP], Manisha Menon[SUP] 1 [/SUP], Kimberly Foster[SUP] 3 [/SUP], Pallab Ghosh[SUP] 3 [/SUP], Kimia Abedi[SUP] 1 [/SUP], Jacob Koster[SUP] 1 [/SUP], Etsuro Nanishi[SUP] 1 2 [/SUP], Lindsey R Baden[SUP] 4 [/SUP], Ofer Levy[SUP] 1 2 5 [/SUP], Thomas VanCott[SUP] 3 [/SUP], Romain Micol[SUP] 3 [/SUP], David J Dowling[SUP] 1 2 [/SUP]
Affiliations
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.
. 2024 Jul 24;16(757):eadm8451.
doi: 10.1126/scitranslmed.adm8451. Epub 2024 Jul 24. Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70
Byron Brook[SUP] 1 2 [/SUP], Valerie Duval[SUP] 3 [/SUP], Soumik Barman[SUP] 1 2 [/SUP], Lauren Speciner[SUP] 3 [/SUP], Cali Sweitzer[SUP] 1 [/SUP], Asad Khanmohammed[SUP] 3 [/SUP], Manisha Menon[SUP] 1 [/SUP], Kimberly Foster[SUP] 3 [/SUP], Pallab Ghosh[SUP] 3 [/SUP], Kimia Abedi[SUP] 1 [/SUP], Jacob Koster[SUP] 1 [/SUP], Etsuro Nanishi[SUP] 1 2 [/SUP], Lindsey R Baden[SUP] 4 [/SUP], Ofer Levy[SUP] 1 2 5 [/SUP], Thomas VanCott[SUP] 3 [/SUP], Romain Micol[SUP] 3 [/SUP], David J Dowling[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39047117
- DOI: 10.1126/scitranslmed.adm8451
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.