Vaccination is one of the strongest tools with regards to fighting infectious diseases. Vaccination is a method of introducing immunization in an individual. It greatly reduces the burden of infectious diseases as it reduces symptomatic disease development as well as prevent further transmission of the vira [1]. This reduces the burden of disease on the national health care systems.

Immune System Response

In all simplicity, immunization is a stimulation of the immune system. This stimulation induces the production of antibodies that can neutralize the stimulus [2]. A vaccine utilizes the immunization that happens when the immune system is exposed to new antigens. However, the infectious agent is replaced with a modified agent that poses as the infectious agent. The modification ensures that no harm or disease is developed. 

The immune stimulation is begun by introducing a modified pathogen (disease inducing organism) to the immune system. This can be done by e.g. injecting an inactivated virus. Different proteins are present on the surface of the pathogen. These allow the pathogen to e.g. adhere to cells in the body and infect the cells [3]. 

Some of these surface proteins are unique for the pathogen in question. These are known as antigens. [4]. These are the particles that the immune system will react to by producing antibodies that are specific to each type of antigen. Each antibody enables the immune system to quickly identify and neutralize any organism that contains the specific antigen on its surface [5].

However, the immune system needs time to react and develop specific antibodies when first exposed to a new antigen. This delay is where the live pathogen has time to multiply and cause symptomatic disease [4]. However, no or only mild disease development occurs if the immune response is triggered by an attenuated or inactivated pathogen as part of a vaccine. If the immune system encounters the antigen again, it is able to immediately confine and destroy the invading organism [6, 7]. This means that any subsequent infection with the same pathogen will result in no or a mild, short course of the disease.

Active Immunization and Vaccine Development

Active immunization has been applied for multiple centuries with the first examples documented in China in the 16th century during a smallpox outbreak [8]. Active immunization at that time was the deliberate exposure of a disease to an individual without modification of the infectious agent. The goal was to induce a mild disease progression while, simultaneously, activating the immune system. This would immunize the subject and prevent smallpox from developing due to any future exposure [8].

A second breakthrough in active immunization arose in the 18th century where vaccines with live, attenuated organisms saw first light [8]. This later progressed into vaccine development based on virus or cell cultures with inactivated disease vectors [8]. 

One of the latest technological approaches to vaccine development is the use of genetic engineering. Genetic manipulation enables the expression of surface proteins from any pathogen, e.g. a virus [2]. The proteins will activate the immune system and immunization process when injected into an individual. The use of genetic engineering thus enables vaccination without introducing the actual pathogen to the vaccine recipient.

mRNA Vaccine Used Against COVID-19

The target antigens of COVID-19 are 180-200 kDa, which corresponds approximately to a size of 5 nm [9]. This means that nanotechnology is needed in order to design a vaccine against COVID-19.

A radically new approach to vaccination has been developed recently. It relies on genetic engineering of mRNA and does not entail introducing any proteins or attenuated pathogens into the body [10]. This means that the vaccine does not cause any disease during the immunization process [11]. This type of vaccine was one of the first COVID-19 vaccine types to be approved for use.

The vaccine consists of a DNA-sequence that encodes the antigen or antigens that are unique to the target pathogen. However, the sequence is injected in the form of mRNA (messenger RNA) which prevents the sequence from permanently integrating itself into the genome of the individual [11,12]. Instead, it only acts as a transient carrier of the genetic information and will degrade over time.

The mRNA in the vaccine enables in situ production of the antigen. This means that the antigen for which the immune response is desired is produced directly in the body of the vaccinated individual. The produced antigen will then trigger the same immune response as if the individual had been exposed to the actual pathogen [11,12]. 

This means that no pathogen – either attenuated or inactivated will ever have entered the body. Instead, the natural protein production environment in our body is used to build the immunization that enables protection against e.g. COVID-19. This also removes the potential side effects of mild symptoms during the immunization process.

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Bibliography

[1] World Health Organization (WHO). “Vaccination greatly reduces disease, disability, death and inequity worldwide.” Bulletin of the World Health Organization, WHO, 2008, Accessed, January 2021, at https://www.who.int/bulletin/volumes/86/2/07-040089/en/.

[2] Murray, Kenneth, et al. “Genetic engineering applied to the development of vaccines.” Philosophical Transactions of the Royal Society of London, B. Biological Sciences, vol. 324, no. 1224, 1989, pp. 461-476.

[3] Science Direct. “Surface Proteins.” Science Direct Topics, Science Direct, 2020, Accessed, January 2021, at https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/surface-proteins.

[4] The Immunisation Advisory Centre. “The immune system and immunisation.” Immunisation, January 2020, accessed, January 2021, at https://www.immune.org.nz/immunisation/immune-system-vaccination.

[5] Britannica. Antibody, accessed, January 2021, at https://www.britannica.com/science/antibody.

[6] Siegrist, Claire-Anne. “Vaccine immunology.” Vaccines, 5 ed., Saunders, 2008, pp. 17-36.

[7] World Health Organization(WHO). “DNA Vaccines.” who.int, WHO, 2007, Accessed, January 2021, at https://www.who.int/teams/health-product-and-policy-standards/standards-and-specifications/vaccines-quality/dna.

[8] Plotkin, Stanley A. History of Vaccine Development. Springer Science & Business Media, 2011.

[9] Huang, Yuan, et al. “Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19.” Acta Pharmacologica Sinica, vol 41, no 9, 2020, pp. 1141-1149.

[10] Bert Hubert, Reverse Engineering the source code of the BioNTech/Pfizer SARS-CoV-2 Vaccine, December 2020, accessed, January 2021, at https://berthub.eu/articles/posts/reverse-engineering-source-code-of-the-biontech-pfizer-vaccine/

[11] Okay, Sezer, et al. “Nanoparticle-based delivery platforms for mRNA vaccine development.” AIMS Biophysics, vol. 7, no. 4, 2020, pp. 323-338.

[12] Schlake, Thomas, et al. “Developing mRNA-vaccine technologies.” RNA Biology, vol. 9, no. 11, 2012, pp. 1319-1330.

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Nanotechnology has multiple research areas that can be utilized in this scientific and technological fight against COVID-19: prevention of dissemination and early diagnosis [1].

Preventing Dissemination

COVID-19 is a respiratory virus infection that is transmitted by contact, droplets and passive carriers such as utensils, light switches or handles that share multiple users [2,3]. The immune system is the primary line of defense for most people, but this is not sufficient for people with compromised immune systems [4]. They instead require e.g. hand sanitizers or face masks as a source of protection.

Chemical disinfectants that can be bought in regular stores can be used for disinfection and sterilization. However, they have limited effect over time and pose a potential risk to public health and the environment [4]. A different method has been proposed: metallic nanoparticles [5,6,7]. 

Metallic nanoparticles are particles of a given metal whose size is on the submicron scale. That is, their diameter is smaller than 0.001 mm (0.00004 inches). This means that their size is comparable to that of a virus particle [8,9]. The interaction between a virus and the nanoparticle depends on which metal is used. One mechanism of action is inactivation of the virus particle before it enters the cells of the human body. The nanoparticle can also stop the viral particle from entering the cell completely [9,10]. This role as an antiviral “doorman” can be due to the binding competition between the virus particle and the nanoparticle – if the nanoparticle binds first, the virus will no longer be able to bind and infect a cell.

The nanoparticles can be incorporated into face masks or can be used for disinfecting air and surfaces to limit the spread of the disease [4]. However, their toxicity must be considered as they can possibly affect human health in larger doses [5].

Diagnosis on the Nanoscale

It is also important to be able to rapidly and accurately diagnose COVID-19. Control measures such as isolation and infection tracking can be initiated and implemented earlier in each case if the detection and diagnosis process is fast. Nanotechnology in the form of nanomaterials can help increase the accuracy and decrease the testing time for a diagnostic process [6].

A nanomaterial is any material that exists on the nanoscale. That means that their defining characteristics also depend on their small size. These properties can be e.g. increased strength or reactivity when compared to the same material at a much larger scale [11]. This means that a sphere of gold or silver can be used for different purposes when it is very small (e.g. a nanoparticle) compared to a larger sphere.

Many nanomaterials are already used for virus detection [6]. Nanomaterials can help early detection as they can facilitate the detection of a target (here – an indicator of COVID-19) even if it is present in much smaller concentrations, i.e. at an earlier time in the infection cycle. The implementation of nanomaterials also requires a smaller sample – and possibly less invasive testing. One advantage of nanomaterials is that they can be designed to have specific desired properties such as optical (interaction with light) or magnetic properties. This means that the materials for diagnosis can be designed to promote a faster and more precise diagnosis [6].

Summary

Nanotechnology can aid the fight against the COVID-19 global pandemic. One aspect is to limit the spread of the disease. This can both be with regards to faster diagnosis (and thus earlier onset of control measures) and more efficient protection measures such as face masks or disinfectants. This means that nanotechnology can help limit the dissemination process and lead to less frequent COVID-19 cases. While it might not completely prohibit the virus from spreading, it can slow the disease down while therapeutic measures and vaccines are being developed.

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Note: Featured image by Fusion Medical Animation on Unsplash

References

[1] Nanotechnology versus coronavirus. Nature Nanotechnology. 15, 617 (2020). https://doi.org/10.1038/s41565-020-0757-7

[2] Subbarao, Kanta, and Siddhartha Mahanty. “Respiratory virus infections: Understanding COVID-19.” Immunity (2020). DOI: https://doi.org/10.1016/j.immuni.2020.05.004

[3] World Health Organization. “Coronavirus disease (COVID-19): Similarities and differences with influenza”. (2020). https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/q-a-similarities-and-differences-covid-19-and-influenza 

[4] Talebian, Sepehr, et al. “Nanotechnology-based disinfectants and sensors for SARS-CoV-2.” Nature nanotechnology 15.8 (2020): 618-621. DOI: https://doi.org/10.1038/s41565-020-0751-0 

[5] Rai, Mahendra, et al. “Metal nanoparticles: The protective nanoshield against virus infection.” Critical reviews in microbiology 42.1 (2016): 46-56. DOI: https://doi.org/10.3109/1040841X.2013.879849 

[6] Campos, Estefânia VR, et al. “How can nanotechnology help to combat COVID-19? Opportunities and urgent need.” Journal of Nanobiotechnology 18.1 (2020): 1-23. DOI: https://doi.org/10.1186/s12951-020-00685-4 

[7] Aderibigbe, Blessing Atim. “Metal-based nanoparticles for the treatment of infectious diseases.” Molecules 22.8 (2017): 1370. DOI: https://dx.doi.org/10.3390%2Fmolecules22081370 

[8] Cuffari, Benedette. “The Size of SARS-CoV-2 Compared to Other Things”. (2020). https://www.news-medical.net/health/The-Size-of-SARS-CoV-2-Compared-to-Other-Things.aspx 

[9] Maduray, Kaminee, and Raveen Parboosing. “Metal Nanoparticles: a Promising Treatment for Viral and Arboviral Infections.” Biological trace element research (2020): 1-18. DOI: https://dx.doi.org/10.1007%2Fs12011-020-02414-2 

[10] Brandelli, Adriano, Ana Carolina Ritter, and Flávio Fonseca Veras. “Antimicrobial activities of metal nanoparticles.” Metal Nanoparticles in Pharma. Springer, Cham, 2017. 337-363. DOI: https://doi.org/10.1007/978-3-319-63790-7_15 

[11] Schwirn, Kathrin, Lars Tietjen, and Inga Beer. “Why are nanomaterials different and how can they be appropriately regulated under REACH?.” Environmental Sciences Europe 26.1 (2014): 4. DOI: https://doi.org/10.1186/2190-4715-26-4 

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