The present invention provides, among other things, a novel and improved method for generating mosaic influenza antigenic polypeptides including hemagglutinin (HA) and neuraminidase (NA) polypeptides based on unique combination of epitope patterns that maximize exposure to epitopes present across multiple HA or NA sequences and therefore improved influenza strain coverage. In particular, the present invention provides engineered H1N1 influenza hemagglutinin (HA) polypeptides that are comprised of novel combinations of protective epitopes and antigenic regions from multiple H1N1 viral strains. Such engineered HA polypeptides have improved properties over HA polypeptides developed through conventional approaches that rely on consensus alignments of viral sequences.

The invention provides a composition useful to prepare high titer influenza viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, and genes from vaccine seed virus isolates which include a HA gene segment with a HA2 sequence encoding a HA2 that confers enhanced growth in cells in culture, such as Vero cells.

The present invention relates to methods of replicating viruses in vitro. In particular, the invention relates to a genetically modified population of cells, and/or a population of cells treated with an exogenous compound, wherein the cells are capable of producing more virus than cells lacking the genetic modification and/or lacking treatment with the exogenous compound. The invention also relates to methods of producing populations of such cells, as well as the use of the viruses obtained to prepare vaccine compositions.

The invention discloses vaccine for coronavirus and influenza virus and method for preparation thereof. More specifically, the invention discloses seasonal viral vaccine i. e. coronavirus and influenza virus vaccine for prophylaxis of novel coronavirus (SARS-CoV-2) infection (COVID-19) and Influenza virus in mammals and method for preparation of such vaccine. The invention discloses the stable combination vaccine compositions of killed-inactivated SARS-CoV-2, Influenza virus (A and B strains) as antigens. The present invention further discloses method of adaptation and growth seasonal influenza (A and B) strains in cell culture and methods of inactivation and purification of influenza virus bulk antigen. The present invention also discloses SARS-CoV-2 vaccine formulation with inactivated Influenza viruses and use of the same to elicit immune response against the SARS-CoV-2 and Influenza viruses in mammals and humans.