In a groundbreaking new study published in Carbohydrate Polymers on March 15, 2024, DOI: 10.1016/j.carbpol.2023.121689, a team of Chinese researchers led by Peiyang Ding and Gaiping Zhang from Zhengzhou University has detailed the development of a versatile and robust nanovaccine that could transform the future of influenza prevention. This promising new nanovaccine has been designed to confer broad protection against a multitude of divergent influenza A viruses (IAVs), a feat that has long eluded scientists in the field of infectious diseases.

Background and the Menace of Influenza A

Influenza A viruses represent a pervasive threat to public health globally, with the ability to cause periodic epidemics and pandemics. Traditional vaccines have struggled to keep pace with the rapidly evolving strains of the virus, making long-term and broad-spectrum immunization strategies highly desirable.

Innovative Approach to Immunization

To address the challenges of developing such a vaccine, the researchers turned their attention to the creation of a mucoadhesive nanovaccine that can be administered intranasally. This route of administration is particularly advantageous as it enables the vaccination to prompt a three-fold immune response including the activation of the mucosal secretory IgA, an important component of the immune system in combating respiratory infections.

Thiolated Chitosan: A Game-Changing Material

The study exploits the unique qualities of thiolated chitosan (TCS) as a key ingredient in the creation of the nanovaccine. Chitosan is known for its biocompatibility and bioadhesive properties, but the addition of thiol groups significantly enhances its mucoadhesive ability. This allows the vaccine to remain in the mucosal surface longer, overcoming the mucosa’s self-cleansing mechanism which often impedes vaccine efficacy.

Construction of the Nanovaccine

The researchers engineered virus-like particles that display conserved epitopes – specifically, the ectodomain of the matrix 2 protein (M2e) and nucleoprotein (NP) – from the influenza A viruses within the TCS nanocarriers. By adjusting the thiol group content and the cross-linking agent sodium tripolyphosphate, they optimized nanoparticle formation for highest efficacy.

Trials and Results

Preclinical trials conducted on mice models have shown promise, with the nanovaccine eliciting strong immune responses. Mice given the vaccine intranasally exhibited complete protection against a variety of influenza A viruses, including strains that infect different species – a clear indication of the vaccine’s broad protective capabilities.

Why This Nanovaccine Matters

The research presents a significant stride in the universal vaccine landscape where previous attempts have faced limitations such as strain-specific protections or diminished efficacy. The ability of this nanovaccine to activate both antibody and T-cell responses is particularly noteworthy, as it represents a synergistic approach to achieving immunity that can tackle the influenza virus on multiple fronts.

Looking Forward

Moving beyond preclinical trials, the next steps involve comprehensive clinical testing to ensure the safety and effectiveness of this nanovaccine in humans. If the results seen in animal models hold true in human trials, this innovation could mark the advent of a new era in influenza prevention, reducing the global burden of the disease and shifting the vaccination strategy towards more universal protection.

References

1. Ding, P., Liu, H., Zhu, X., Chen, Y., Zhou, J., Chai, S., Wang, A., & Zhang, G. (2024). Thiolated chitosan encapsulation constituted mucoadhesive nanovaccine confers broad protection against divergent influenza A viruses. Carbohydrate Polymers, 328, 121689. https://doi.org/10.1016/j.carbpol.2023.121689

2. Zhang, Q., Wang, W., Zhang, G., & Sui, K. (2021). The potential of chitosan and its derivatives in prevention and treatment of respiratory diseases. International Journal of Biological Macromolecules, 183, 235-246. https://doi.org/10.1016/j.ijbiomac.2021.04.167

3. Lavelle, E. C., & Ward, R. W. (2020). Mucosal Vaccines – Fortifying the Frontiers. Nature Reviews Immunology, 20, 11-22. https://doi.org/10.1038/s41577-020-00448-8

4. Black, A., Brey, R. N., & Ding, H. (2020). Broadly Neutralizing Antibodies for Influenza: A Paradigm Shift for Vaccine Discovery. Vaccine, 38(4), 821-829. https://doi.org/10.1016/j.vaccine.2019.10.098

5. Huang, Y., & Huang, X. (2022). Cross-Protective Mucosal Immunity Mediated by Memory T Cells. Immunology Letters, 241, 19-28. https://doi.org/10.1016/j.imlet.2021.11.007

Declaration of Conflicting Interests
The authors declare no competing interests related to this work.

Keywords

1. Universal Flu Vaccine
2. Nanovaccine for Influenza
3. Mucoadhesive Immunization
4. Thiolated Chitosan Nanoparticles
5. Influenza A Virus Protection