Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses

Abstract

Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets

“…Cell transfection of HEK293T cells was performed with TransIT-mRNA (Mirus Bio, Madison, WI) as described before ( 44 ). Briefly, mRNA (0.3 μg) was combined with TransIT-mRNA Reagent (0.34 μl) and Boost Reagent (0.22 μl) in 17 μl of serum-free medium, and the complex was added to 6 × 10 4 cells in 183 μl of complete medium.…”

“…In addition, mRNA-LNP vaccines can be rapidly produced and are easily adjusted to new emerging viral variants (39). Multiple influenza vaccines based on mRNA-LNP are currently in development, with promising early results (40)(41)(42)(43)(44). These vaccines, however, primarily focus on inducing humoral responses, without fully using the potential of T cell immunity against conserved internal influenza proteins.…”

Multivalent Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccines Demonstrate a Greater Breadth in T cell but not Antibody Responses

“…vaccine 34 . Indeed, the generation of multivalent mRNA-LNP vaccines proved to be a promising strategy for the development of broadly protective influenza virus vaccines 35,36 .…”

“…Additionally, the mRNA-LNP vaccine possesses multiple advantages, including a favorable safety profile, presentation of immunogens on the cell surface, rapid and cost-effective manufacturing process, and the ease of combining multiple antigens into a single vaccine 34 . Indeed, the generation of multivalent mRNA-LNP vaccines proved to be a promising strategy for the development of broadly protective influenza virus vaccines 35, 36 . Our lab previously compared the immunogenicity of the mRNA-LNP delivery platform to the protein-based full-length or ectodomain platform with squalene-like adjuvants encoding full-length HCMV gB genotype 1 (gB-1, sequence from Towne strain, GenBank accessioning number: FJ616285.1) in a rabbit model.…”

Multivalent Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccines Demonstrate a Greater Breadth in T cell but not Antibody Responses

“…Additionally, the mRNA-LNP vaccine possesses multiple advantages, including a favorable safety profile, presentation of immunogens on the cell surface , rapid and costeffective manufacturing process, and the ease of combining multiple antigens into a single vaccine 34 . Indeed, the generation of multivalent mRNA-LNP vaccines proved to be a promising strategy for the development of broadly protective influenza virus vaccines 35,36 .…”