Transient inhibition of type I interferon enhances CD8+ T cell stemness and vaccine protection.

Developing vaccines that promote CD8+ T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1+ stem cell-like memory CD8+ T (TSCM) cells are important determinants of long-lived memory. Yet, the developmental requirements for TSCM cell formation are unclear.

An LNP-mRNA vaccine modulates innate cell trafficking and promotes polyfunctional Th1 CD4 T cell responses to enhance BCG-induced protective immunity against Mycobacterium tuberculosis.

Background: Mycobacterium tuberculosis remains the largest infectious cause of mortality worldwide, even with over a century of widespread administration of the only licenced tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG). mRNA technology remains an underexplored approach for combating chronic bacterial infections such as TB.

Methods: We have developed a lipid nanoparticle (LNP)-mRNA vaccine, termed mRNA, encoding for the M.

mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting.

We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.

Conversion of vaccines from low to high immunogenicity by antibodies with epitope complementarity.

Existing antibodies (Abs) have varied effects on humoral immunity during subsequent infections. Here, we leveraged in vivo systems that allow precise control of antigen-specific Abs and B cells to examine the impact of Ab dose, affinity, and specificity in directing B cell activation and differentiation. Abs competing with the B cell receptor (BCR) epitope showed affinity-dependent suppression.

Replacing poly(ethylene glycol) with RAFT lipopolymers in mRNA lipid nanoparticle systems for effective gene delivery.

Lipid nanoparticles (LNPs) have emerged as promising carriers to efficiently transport mRNA into cells for protein translation, as seen with the mRNA vaccines used against COVID-19. However, they contain a widely used polymer - poly(ethylene glycol) (PEG) - which lacks the functionality to be easily modified (which could effectively control the physicochemical properties of the LNPs such as its charge), and is also known to be immunogenic. Thus, it is desirable to explore alternative polymers which can replace the PEG component in mRNA LNP vaccines and therapeutics, while still maintaining their efficacy.