Recombinant protein vaccines, such as the Novavax vaccine used to fight COVID-19, offer several advantages over conventional vaccines.
They are easy to precisely manufacture. They are safe and potentially more effective. And they may require smaller doses.
Because of these characteristics, there is great interest in the development of recombinant influenza vaccines. To date, however, the Food and Drug Administration has approved only one such vaccine.
A University at Buffalo-led research team hopes to add to that number. He is developing a new recombinant flu vaccine – described in a study published today in the journal Cell Reports Medicine – which has the potential to compete with existing vaccines.
Due to the variable nature of the viruses that cause influenza, current vaccines are not optimally effective in the entire population. We believe our vaccine candidate has the potential to improve this by inducing stronger and broader immunity and reducing the likelihood of disease and death.”
Jonathan Lovell, Ph.D., senior study co-author, SUNY Empire Professor of Innovation in the Department of Biomedical Engineering at UB
Conventional flu vaccines either contain inactivated germs that cause flu or are based on weakened forms of the disease. They are made using fertilized chicken eggs or, less commonly, by cell culture-based production.
The vaccine the UB-led team is developing is based on a nanoliposome — a tiny spherical sac — created by Lovell and colleagues called cobalt-porphyrin-phospholipid, or CoPoP. The CoPoP platform enables immune response-promoting proteins to be displayed on the surface of the nanoliposome, resulting in potent vaccine efficacy.
(Although not part of this study, the CoPoP vaccine platform has passed Phase 2 and Phase 3 clinical trials in South Korea and the Philippines as a candidate for a vaccine against COVID-19. This is a partnership between UB spinoff company POP Biotechnologies, co-founded by Lovell and the South Korean biotech company EuBiologicks.)
By themselves, these nanoliposomes do not fight disease. But when combined with recombinant flu proteins, which can be generated based on genetic information from viruses, they boost the immune system’s response to the disease.
In the new study, the team attached a total of six proteins to the nanoliposome – three each from two different protein groups, hemagglutinins and neuraminidase. The team also added two adjuvants (PHAD and QS21) to boost the immune response.
The researchers evaluated the resulting “hexaplex” nanoliposome in animal models with three common influenza strains: H1N1, H3N2 and type B.
Even when administered at low doses, nanoliposome hexaplex provides superior protection and survival against H1 and N1 compared to Flublok, the only licensed recombinant influenza vaccine in the US, and Fluaid, an egg-based vaccine. The tests showed comparable levels of protection against H3N2 and type B viruses.
Tests were performed by vaccination and by transfer of blood serum from vaccinated mice to unvaccinated mice.
“The combination of the two groups of proteins resulted in synergistic effects. In particular, adjuvant nanoliposomes excelled in producing functional antibodies and activating T cells, which are critical for combating serious influenza infection,” said lead author Zachary Xia, a postdoctoral fellow in Lovell’s lab.
Bruce Davidson, MD, research associate professor of anesthesiology at UB’s Jacobs School of Medicine and Biomedical Sciences, is senior co-author of the study.
He says that “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. This is critical not only for the flu, but also for potential outbreaks like what we saw with COVID-19. There is still much work to be done to fully test and validate this influenza technology, but at this stage these early results are quite promising.”
In addition to UB, study co-authors include scientists from McGill University.
Patents related to this work have been filed with the Research Foundation for the State University of New York. Lovell and study co-author Wei-Qiao Huang, a postdoctoral fellow in Lovell’s lab, are employed by POP Biotechnologies.
The study was funded in part by the National Institutes of Health.
source:
Journal reference:
Siya, ZR, and others. (2024) Adjuvanted Nanoliposomes Displaying Six Hemagglutinins and Neuraminidases as an Influenza Virus Vaccine. Cell Reports Medicine. doi.org/10.1016/j.xcrm.2024.101433.
