Engineered bacteria are provided that produce modified lipid A and a polypeptide or polysaccharide antigens. In some aspects, immunogenic compositions are provided comprising a modified a lipid A and a polypeptide or polysaccharide antigen.

In some embodiments the present invention provides influenza hemagglutinin (HA) polypeptides, proteins, and protein complexes that comprise a stalk domain that is engineered to facilitate maintenance of its native trimeric conformation, even if the head domain of the HA protein is removed or disrupted. In some embodiments, the present invention provides compositions comprising such polypeptides, proteins, and protein complexes, and methods of use of such proteins and compositions, for example as vaccine immunogens.

The present invention provides protein libraries comprising variants of an antigenic viral protein that each have a different set of mutations at one or more hypervariable sites. Nucleic acid and vector libraries encoding the protein libraries, vaccines comprising the libraries, and methods of inducing an immune response against the antigenic viral protein are also provided.

The invention provides a composition useful to prepare high titer influenza B viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza B virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, that confer enhanced growth in cells in culture, such as MDCK cells, or in eggs.

The invention provides a composition useful to prepare high titer influenza B viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza B virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, that confer enhanced growth in cells in culture, such as MDCK cells, or in eggs.

The disclosure provides a sub-micron particle comprising a first payload molecule, a lipid structure and a plurality of amphiphilic polymer chains surrounding the lipid structure. The first payload molecule is a macromolecule, optionally a nucleic acid. Additionally, the hydrophobicity of the amphiphilic polymer chains changes in response to an external stimulus.

The present disclosure provides vaccine compositions comprising a plurality of distinct antigens. Also provided are nucleic acid vaccine composition comprising one or more nucleic acids encoding for a plurality of distinct antigens. The plurality of distinct antigens comprises a combination of influenza antigens. The vaccine composition can be formulated for delivery as a mRNA/LNP, a recombinant protein, a virus-like particle (VLP), or DNA. Methods of preventing an influenza infection and methods of inducing an immune response are also disclosed.