A Trivalent Virus-Like Particle Vaccine Elicits Protective Immune Responses against Seasonal Influenza Strains in Mice and Ferrets

Abstract

There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.

Trichoplusia ni cells (High FiveTM) are highly efficient for the production of influenza A virus-like particles: a comparison of two insect cell lines as production platforms for influenza vaccines

“…Until now, production of insect cell derived influenza VLP vaccines has been carried out in Sf9 cells [13][14][15][16][17][18][19][20]. We conclude from our results that BTI-TN5B1-4 cells are an advantageous production system for influenza VLPs as it decreases the baculovirus background and therefore DNA contamination.…”

“…VLPs of influenza subtypes H1, H3, H5 and H9 have been generated in insect cells by co-expression of HA, NA, M1 and M2 or HA, NA and M1 or by co-expression of HA and M1, respectively [13][14][15][16][17][18][19][20]. Immunological studies with all of these subtypes have shown superior immune responses against influenza A when administered intranasally, intraperitoneally or intramuscularly [11,[13][14][15][16][17][18]20]. Up to date all of these studies have been carried out with VLPs that had been produced in the Spodoptera frugiperda insect cell line Sf9.…”

Microneedle Delivery of H5N1 Influenza Virus-Like Particles to the Skin Induces Long-Lasting B- and T-Cell Responses in Mice

“…Virus-like particles (VLPs) have been suggested as a promising candidate vaccine against influenza viruses. Such influenza VLPs have been demonstrated to provide protective immunity in experimental animal models (12,15,19,37,44), and VLP vaccines against other diseases are in widespread clinical use (18).…”

Mucosal Adjuvants for Influenza Virus-Like Particle Vaccine

“…Influenza VLP vaccines have been shown to induce protection, suggesting that VLPs can be a promising vaccine candidate (2,7,10,12,29,31,34). Immune responses after mucosal immunization are relatively low (32).…”