Building on the success of lipid nanoparticle mRNA vaccines in the recent SARS-CoV-2 pandemic, Brook and Duval et al. addressed waning immunity and durability in older adults. To boost immunogenicity, a scIL-12 p70 molecular adjuvant, engineered with a multiorgan protection sequence (MOP), which binds microRNAs to limit expression to muscle cells at the injection site, was given to young adult and older mice (>10 months) with the BNT162b2 SARS-CoV-2 vaccine. Humoral and cellular immune responses to the spike protein were comparable in both young and old groups, and were significantly amplified with increased durability for one year.
Contributed by Katherine Turner
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.
Author Info: (1) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Author Info: (1) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. (2) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (3) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. (4) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (5) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. (6) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (7) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. (8) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (9) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (10) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. (11) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. (12) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. (13) Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. (14) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. (15) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (16) Combined Therapeutics Incorporated, Boston, MA 02135, USA. (17) Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
