DEVELOPMENT OF SEASONAL INFLUENZA VIRUS-LIKE PARTICLE (VLP) VACCINES USING INSECT CELL-BASED BACULOVIRUS EXPRESSING SYSTEM

Abstract

Intro: Influenza viruses are highly infectious and cause widespread respiratory diseases. Moreover, it could pose a noteworthy epidemic and pandemic threat to public health. Vaccination is the most cost-effective intervention to prevent influenza and its complications. Currently, most commercial influenza vaccines are produced using embryonic chicken eggs (ECE), which is hard to scale up efficiently and could potentially reduce vaccine efficacy due to gene mutations in HA genes. In addition, the egg-based technology is associated with some jeopardy of allergic reactions and there is a risk of disrupted egg supply when avian influenza outbreaks erupt. To overcome the dependency on ECE, developments of influenza vaccines based on efficient and robust production platforms are urgently needed. Methods: Several potential vaccine production systems already have shown potential as replacers, including a virus-like particle (VLP) platform. In the current study, using a Baculovirus Expression System (BES), we engineered HA, NA, and M1 genes of influenza A/H1N1, A/H3N2, B/Yamagata-like, and B/Victoria-like virus strains (A/Hawaii/70/2019, A/Minnesota/41/2019, B/Brisbane/09/2014 & B/Brisbane/63/2014) to produce VLP vaccine antigens H1N1-VLP, H3N2-VLP, Yamagata-VLP, Victoria-VLP, respectively. Then functional and antigenic features were determined, including hemagglutination assay, protein composition, size, and morphology of the VLP antigens. Findings: We found that these recombinants VLPs contained influenza HA, NA, and M1 with functional activity, resembled influenza virions in morphology and size, and were structurally intact. We compared the immunogenicity of in-house VLP antigens and commercial recombinant HA (rHA) vaccines in mice. Results revealed that our recombinant VLP antigens are highly immunogenic and produced higher hemagglutination inhibition and virus neutralization antibody titers than the commercial rHA vaccine. Conclusion: The insect cell-based seasonal influenza VLP vaccine antigens are more immunogenic than rHA antigens. Further animal challenge studies are worth to conduct.