Development of a new recombinant flu vaccine

Scientists from the University at Buffalo (UB) and McGill University have developed a new recombinant flu vaccine which shows promising results and could compete with existing vaccines. Recombinant protein vaccines, such as the Novavax vaccine used for COVID-19, provide several advantages over conventional vaccines. They are safer and possibly more effective, easier to precisely produce, and require smaller doses. However, to date, the Food and Drug Administration (FDA) has approved only one such vaccine.

Dr Jonathan Lovell, senior co-author of the study and SUNY Empire Innovation Professor in the Department of Biomedical Engineering at UB explained: “Because of the variable nature of the viruses that cause influenza, current vaccines are not optimally effective among the overall population. We believe our vaccine candidate has the potential to improve upon this by inducing stronger and broader immunity and reducing the likelihood of illness and death.”

Conventional flu vaccines are based on weakened forms of the disease or contain deactivated microbes that cause influenza. Typically, they are made using fertilised chicken eggs or, less commonly, through cell culture-based production. However, the UB-led vaccine is based on a nanoliposome created by the team, named cobalt-porphyrin-phospholipid (CoPoP). The CoPoP platform enables immune response by promoting proteins to be displayed on the surface of the nanoliposome, resulting in potent vaccine efficacy.

Combining the nanoliposomes with recombinant influenza proteins, that can be generated based on genetic information from viruses, enhance the immune system’s response to disease. The researchers attached a total of six proteins to the nanoliposome: three each from two different protein groups, hemagglutinins and neuraminidases. Also, they added two adjuvants, PHAD and QS21, to boost immune response, and then evaluated the resulting “hexaplex” nanoliposome in animal models with three common flu strains: H1N1, H3N2 and type B.

The hexaplex nanoliposome provided superior protection and survival from H1 and N1 even when administered in low doses, when compared to Flublok, the sole licensed recombinant influenza vaccine in the US, and Fluaid, an egg-based vaccine. Tests, which were conducted via vaccination and through blood serum transfer from vaccinated mice into non-vaccinated mice, demonstrated comparable levels of protection against H3N2 and type B viruses.

Lead author Zachary Sia, a PhD candidate in Lovell’s lab, commented: “The combination of the two groups of proteins led to synergistic effects. In particular, the adjuvanted nanoliposomes excelled in the production of functional antibodies and the activation of T cells, which are critical to fighting off serious infection of the flu.”

Dr Bruce Davidson, co-author of the study and research associate professor of anaesthesiology in the Jacobs School of Medicine and Biomedical Sciences at UB, added: “using not only hemagglutinin but also neuraminidase antigens to create vaccines is important because it translates into broader immunity and companies will be able to create more doses with less materials. That’s critical for not only the flu but also potential outbreaks like what we saw with COVID-19. There is still much work to be done in fully testing and validating this flu technology, but at this point these early results are quite promising.”

This study was published in Cell Reports Medicine.