The influenza virus, a shape-shifting foe, has plagued humanity for centuries. Current flu vaccines offer protection, but their efficacy varies year to year because they must be reformulated annually to match the circulating strains[1]. This has spurred researchers to pursue a “universal” flu vaccine that would provide broad and long-lasting protection against all influenza strains[1]. Designer proteins, created from scratch in the lab, are emerging as a promising tool in this quest.
The Designer Protein Approach to Flu Vaccines
Traditional flu vaccines contain weakened or inactivated influenza viruses or specific proteins from those viruses, such as hemagglutinin (HA)[5]. However, because the virus mutates so quickly, predicting which strains will pose the biggest risk and choosing which ingredients to include is a guessing game[1].
Designer proteins offer a new approach. Researchers are using computational methods, like COBRA (Computationally Optimized Broadly Reactive Antigens), to analyze thousands of genetic sequences of influenza strains and identify conserved regions – amino acid sequences that remain relatively constant across different viruses and seasons[1]. These conserved regions can then be incorporated into designer proteins that serve as universal vaccine candidates[1].
Key Strategies in Designer Protein Flu Vaccine Development:
- HA Stem-Based Vaccines: Research has focused on using the hemagglutinin (HA) stem as an antigen for a universal flu vaccine[4]. The HA stem is more conserved than the HA head, making it a more attractive target for broadly neutralizing antibodies[4].
- Mosaic HA Immunogens: This strategy involves linking HA proteins from different influenza strains together to create mosaic HA immunogens, which elicit antibodies capable of neutralizing diverse influenza viruses[6].
- Nanoparticle Vaccines: Protein Design is using protein design to create custom protein nanoparticles that can be decorated with different viral proteins[2]. These vaccines allow the immune system to see up to 60 different strains of a pathogen at once, which may lead to better protection[2]. One example is FluMos-v1, an experimental nanoparticle vaccine for the flu that is now in Phase 1 clinical trials[2].
Progress and Promise
Researchers at Cleveland Clinic’s Lerner Research Institute have reported that their universal flu vaccine candidate, tested on animal models, elicited a strong immune response and provided protection against severe infection after viral exposure[1]. The vaccine candidate incorporates proteins from 8 strains of influenza[1]. The researchers administered the vaccine candidate intranasally to mice, and blood tests showed that 4 weeks later the animals had developed antibodies against the virus[1]. When the mice were exposed to the pathogen, they were protected against developing infection[1]. According to virologist Naoko Uno, Ph.D., who led the study, the researchers hope to launch human clinical trials within 1-3 years[1].
Challenges and Future Directions
While the development of designer protein-based universal flu vaccines is promising, several challenges remain. A vaccine mix would then need to be tested in a large-scale, multiyear study designed to show that the vaccine candidate works better than the seasonal vaccine[5].
Despite these challenges, the progress in designer protein-based universal flu vaccines is encouraging. As research continues, these innovative vaccines hold the potential to provide broad and long-lasting protection against influenza, revolutionizing how we combat this persistent global threat. The COBRA methodology might be used to analyze mRNA or other biomolecules or explored for developing vaccines to viral diseases, like dengue[1].
Citations:
[1] https://asm.org/press-releases/2024/august/universal-flu-vaccine-candidate-protects-against-i
[2] https://www.ipd.uw.edu/2023/07/designing-better-flu-shots-nih-highlights-king-labs-progress-on-universal-vaccines/
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC9415875/
[4] https://en.wikipedia.org/wiki/Universal_flu_vaccine
[5] https://www.science.org/content/article/innovative-universal-flu-vaccine-shows-promises-it-first-clinical-test
[6] https://www.niaid.nih.gov/diseases-conditions/designer-flu-proteins-universal-influenza-vaccines
[7] https://ivr.cidrap.umn.edu/universal-influenza-vaccine-technology-landscape
