Enhancing TB Vaccines with Nanotechnology

Tuberculosis (TB), a highly infectious bacterial disease caused by Mycobacterium tuberculosis (Mtb), has been a significant burden on global health and the economy for many decades.

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According to the World Health Organization, around 10 million people contract TB annually, and 1.5 million die from it, making it the deadliest infectious disease worldwide, second only to COVID-19 between 2020 and 2022.²

Today, the standard TB treatment initially involves a mix of first-line drugs such as isoniazid, rifampicin, ethambutol, and streptomycin.³ In cases of relapse and further spread, second-line drugs such as amikacin, kanamycin, and capreomycin are administered.³

However, the effectiveness of these drugs has diminished over time due to the spread of multidrug-resistant and extensively drug-resistant strains of the pathogen, highlighting the urgent need for new treatment strategies.⁴

Well-known TB vaccines are effective in preventing severe TB in children under five, but their effectiveness decreases in teenagers and adults and varies among different ethnic groups.⁵ The long-term effectiveness of the vaccine and its ability to prevent new infections remain concerns. To address these issues, nanotechnology is aiding the transformation of TB vaccination.

Nanotechnology and TB Treatment

Nanotechnology-assisted methods offer several advantages over conventional drugs and vaccination in TB treatment. For instance, they enhance the targeting and delivery of TB antigens using carrier-based drug delivery systems.⁶

Deoxyribonucleic acid (DNA) vaccination, which involves inserting a gene encoding a specific antigen into a plasmid, also benefits from nanomaterials such as nanoparticles, liposomes, and virus-like particles.⁷ These materials ensure controlled drug release, delivering therapeutic agents directly to TB bacteria reservoirs and improving drug bioavailability and protection against degradation.

Nanoscale adjuvants have significantly improved vaccination methods by enhancing immune responses.⁸ These adjuvants, like AS02, have shown effectiveness in eliciting strong antibody and cell-mediated immune responses, making them efficient TB vaccines.⁸

Biodegradable polymers, liposomes, and microspheres reduce drug doses and treatment duration by delivering high concentrations with low toxicity.⁶

Nanosized particles, especially for inhalation, allow for rapid absorption and high lung bioavailability, reducing drug doses and systemic side effects.⁹ This approach is particularly effective for targeting bacterial reservoirs, like alveolar macrophages, improving patient adherence and treatment outcomes.¹⁰

Advantages of Nanotechnology-enhanced TB Vaccination

Nanotech-enhanced TB vaccines offer superior effectiveness and longer-lasting immunity compared to traditional vaccines. By facilitating controlled drug release, nanoparticles reduce dosing frequency, enhance patient compliance, and maintain therapeutic levels with fewer administrations.¹¹

These materials interact with various immune cells over extended periods, boosting the quality of immune responses as the vaccine reaches lymphoid tissues. For instance, vaccines incorporating iron oxide nanoparticles and TB antigens have shown robust immune responses and reduced lung bacterial loads in animal studies, while ‘cationic liposomes’ improve vaccine efficacy and durability.¹²

Nanotechnology intervention helps significantly lower drug dosage and potential side effects in TB vaccines. Natural polymers like chitosan and synthetic materials such as poly(lactide-co-glycolide) control drug release rates, minimize adverse side effects and optimize treatment outcomes, effectively addressing drug resistance challenges.¹²

Advancements in nanotechnology also enable the versatile delivery of TB vaccines through oral and inhalable routes. Oral formulations like chitosan nanoparticles ensure encapsulation of the drugs, thereby increasing their effectiveness.¹¹

Inhalable nanocarriers, such as poly(amidoamine) dendrimers and graft-copolymers, provide targeted lung delivery, enhancing therapeutic efficacy and improving patient adherence.¹¹

Challenges and Considerations in Nanotechnology-based TB Vaccination

Developing nanotechnology-based vaccines for TB presents several technical and manufacturing challenges. These include ensuring the stability and reproducibility of nanocarriers during production, which is crucial for maintaining vaccine efficacy.

Nanoparticle formulations must be precisely engineered to achieve optimal drug release profiles and immune responses.¹³ Scaling up production while ensuring quality and batch-to-batch uniformity is also challenging.

Safety and regulatory hurdles are other major considerations in advancing nanotech-based TB vaccines. Regulatory agencies require rigorous testing to ensure the safety and efficacy of these novel formulations.¹²

Safety concerns arise due to nanoparticle toxicity and long-term health effects, especially via inhalation or oral routes.⁷ Establishing clear guidelines for assessing nanomaterial biocompatibility and risks in vaccines is crucial.

Cost and scalability issues present significant barriers to the widespread implementation of nanotechnology-based TB vaccines. Producing nanocarriers can be expensive due to the requirement for specific materials (like lyoprotectants and other additives) and specialized technology.¹²

Scaling up manufacturing processes to meet global demand while keeping vaccines affordable and accessible to vulnerable populations in TB-endemic regions remains challenging. Overcoming these economic challenges requires innovative financing models and partnerships to support research, development, and production infrastructure.

Future Outlook

The future of TB vaccination strategies enhanced by nanotechnology holds promising prospects driven by ongoing research and potential breakthroughs. Researchers are exploring various nanomaterials like polymer nanoparticles, lipid carriers, and virus-like particles to improve TB vaccines.¹²

These nanotechnologies aim to enhance immune responses by precisely targeting antigen delivery and promoting efficient uptake by immune cells like dendritic cells.¹⁴ Innovations like electroporation and microneedle systems further enhance vaccine delivery efficiency, potentially reducing vaccine doses and enhancing patient compliance.⁷

The ability of nanomaterials to stimulate strong cellular and humoral immune responses could lead to vaccines capable of more effectively preventing TB infection and progression than current methods.

The adaptability of nanotechnology in vaccine development may also pave the way for broader applications in global health strategies, potentially influencing future vaccine formulations for diseases other than TB.

Nanotechnology-based TB vaccination strategies represent a promising frontier in global health. While nanotechnology holds promise for revolutionizing TB vaccine development, several challenges must be addressed. These include overcoming technical hurdles in manufacturing, ensuring safety and regulatory compliance, and addressing cost and scalability issues.

Collaboration across sectors and disciplines is crucial to advancing research, conducting effective preclinical studies, and securing adequate financial support. Addressing these challenges in nanotech-based TB vaccines could significantly aid global efforts to combat tuberculosis.

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 References and Further Reading

1. Gengenbacher, M., Kaufmann, SH. (2012). Mycobacterium tuberculosis: success through dormancy. FEMS microbiology reviews. DOI: 10.1111/j.1574-6976.2012.00331
2. Kiziltaş, Ş., Babalik, A. (2023). Tuberculosis: An Overview. Airway diseases. Available at: https://link.springer.com/chapter/10.1007/978-3-031-22483-6_40-1
3. National Library of Medicine (2008). Treatment of Tuberculosis Patients [online] World Health Organization. Available at: https://www.ncbi.nlm.nih.gov/books/NBK310759
4. Stephanie, F., Saragih, M., Tambunan, USF. (2021). Recent progress and challenges for drug-resistant tuberculosis treatment. Pharmaceutics, 13(5). DOI: 10.3390/pharmaceutics13050592
5. Choudhary, S., Devi, VK. (2015). Potential of nanotechnology as a delivery platform against tuberculosis: current research review. Journal of controlled release, 202, pp.65-75. DOI: 10.1016/j.jconrel.2015.01.035
6. Nasiruddin, M., Neyaz, MK., Das, S. (2017). Nanotechnology‐based approach in tuberculosis treatment. Tuberculosis research and treatment. DOI: 10.1155/2017/4920209
7. Luo, X., et al., (2022). Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape. Drug Delivery. DOI: 10.1080/10717544.2022.2120565
8. Gupta, A., Das, S., Schanen, B., Seal, S. (2016). Adjuvants in micro‐to nanoscale: current state and future direction. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. DOI: 10.1002/wnan.1354
9. Costa, A., Pinheiro, M., Magalhães, J., Ribeiro, R., Seabra, V., Reis, S., & Sarmento, B. (2016). The formulation of nanomedicines for treating tuberculosis. Advanced drug delivery reviews, 102, pp.102-115. DOI: 10.1016/j.addr.2016.04.012
10. Huang, Z., Kłodzińska, S. N., Wan, F., & Nielsen, H. M. (2021). Nanoparticle-mediated pulmonary drug delivery: State of the art towards efficient treatment of recalcitrant respiratory tract bacterial infections. Drug delivery and translational research. DOI: 10.1007/s13346-021-00954-1
11. Dahanayake, M. H., & Jayasundera, A. C. (2021). Nano-based drug delivery optimization for tuberculosis treatment: A review. Journal of Microbiological Methods. DOI: 10.1016/j.mimet.2020.106127
12. Chopra, H., et al. (2023). An insight into advances in developing nanotechnology based therapeutics, drug delivery, diagnostics and vaccines: multidimensional applications in tuberculosis disease management. Pharmaceuticals. DOI: 10.3390/ph16040581 
13. Mitchell, MJ., Billingsley, MM., Haley, RM., Wechsler, ME., Peppas, N. A., & Langer, R. (2021). Engineering precision nanoparticles for drug delivery. Nature reviews drug discovery. DOI: 10.1038/s41573-020-0090-8
14. Baranyai, Z, et al. (2021). Nanotechnology‐based targeted drug delivery: an emerging tool to overcome tuberculosis. Advanced Therapeutics. DOI: 10.1002/adtp.202000113

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