key: cord-0857399-wdsibhv4 authors: Shapiro, Robert S. title: COVID‐19 vaccines and nanomedicine date: 2021-06-05 journal: Int J Dermatol DOI: 10.1111/ijd.15673 sha: ecb2661f33ddd6adffb2dcd8c4c50592f18f34ea doc_id: 857399 cord_uid: wdsibhv4 BACKGROUND: The COVID‐19 virus‐induced pandemic has been the deadliest pandemic to have occurred in two generations, besides HIV/AIDS. Epidemiologists predicted that the SARS‐Cov 2 pandemic would not be able to be brought under control until a majority of the world’s population had been inoculated with safe and effective vaccines. A world‐wide effort to expedite vaccine development was successful. Previous research for vaccines to prevent SARS and MERS, also coronaviruses, was vital to this success. Nanotechnology was essential to this vaccine development. Key elements are presented here to better understand the relationship between nanomedicine and the COVID‐19 vaccine development. METHODS: NLM PubMed searches for COVID‐19 vaccines, nanotechnology and nanomedicine were done. There were 6911 articles screened, 235 of which were deemed appropriate to this subject and utilized here, together with two landmark nanomedicine texts used to expand understanding of the basic science of nanotechnology. RESULTS: SARS‐Cov 2, caused by the COVID‐19 virus, was first recognized in China in December of 2019 and was declared as a pandemic in March of 2020. The RNA sequence was identified in January of 2020. Within 4 months of the viral genome being released, over 259 vaccines had been in development. The World Health Organization (WHO) anticipated a vaccine with a 50‐80% efficacy to be developed within 1‐2 years. Ahead of schedule, the Food and Drug Administration (FDA) announced the emergency authorization approval for two mRNA vaccines within 11 month’s time. Nanotechnology was the key to the success of these rapidly developed, safe and effective vaccines. A brief review of pertinent basic science principles of nanomedicine are presented. The development of COVID vaccines is reviewed. Future considerations are discussed. CONCLUSIONS: Control of the COVID‐19 SARS‐Cov2 pandemic benefitted from nanomedicine principles used to develop highly effective, yet very safe and relatively inexpensive vaccines. These nanovaccines can be much more easily altered to adjust for viral variants than traditional live or inactivated legacy‐type whole virus vaccines. why can we not cure the common cold, 20% of which are due to a coronavirus? 7, 8 The coronavirus was first discovered in the same decade as men walked on the moon. 7 This was in a time before fax machines or microwave ovens, in the days of giant room-sized mainframe computers that were capable of an infinitesimally small functional capability compared to a current smart phone. The nascent space technology was sufficient for moon walking in the 1960s; however, until the human genome project and the development of biotechnology and nanotechnology, there was no remote possibility of attempting to cure the common cold. Segueing into the 21st century, the cold war has fortunately been transformed into a more societally beneficial and peaceful "cold" race for a COVID-19 vaccine. The Russian COVID-19 vaccine, named SPUTNIK V, has arrived 9 (without completing the third phase of more widespread testing 10 ) several months in advance of the first two U.S. mRNA nanovaccines. One of the most important issues regarding the severity of the COVID-19 pandemic relates to the high Ro, 1, 11 which is due to the high degree of contagion of asymptomatic patients. The immunopathology of COVID-19 is not fully understood. The virus has many mechanisms of immune evasion. 10, 12 Critically, there is asynchrony 13 and dysfunction 8, 14 of the patient's immune system, leading to hypercytokinemia, 15 Nano is defined as size equal to or less than 100 nm. Visible light has a wavelength of 400-700 nm. Nanoparticles approach molecular sizes (1000 nm = 1 micron) (500 Daltons =~2.5 nm). Particles that are close to molecular size do not act in the same way as their micro or macro forms. It is analagous the phase differences of solid, liquid, gas, plasma, as well as the differences between astronomic bodies and subatomic particles. For instance, carbon 22 and salt are electrical conductors as nanoparticles. Gold is a liquid as a nanoparticle. 23 Glass is flexible in nanoparticle sizes. The interparticle interactions, surface attractions, ionization potential, surface reactivity, and magnetism all change when materials approach molecular dimensions. Fifteen and 50 nm gold nanoparticles can easily penetrate the blood brain barrier 24 We are familiar with nanosized zinc and titanium as they comprise sunscreens, which are translucent, because their nanosizes are below the wavelength of light. The U.S. government allows nanozinc and nanotitanium to pass as "generally accepted as safe," based on macro and micro zinc oxide and titanium dioxide. This is illogical, because they do not act the same in the nano form as in the micro and macro forms. A thousand tons of titanium dioxide and zinc oxide are produced annually. Seventy percent of titanium dioxide and 30% of zinc oxide sunscreens contain nanoparticles. Titanium dioxide nanoparticles can cause DNA damage 26 and adduct formation. 27 With exposure to UV light, free radicals are generated. 28 Titanium dioxide nanoparticle agglomerates have been observed in intracellular organelles. 29 Zinc oxide nanoparticles have the potential to damage DNA. 30 Sunscreen containing zinc nanoparticles applied to humans has been shown to increase serum levels of zinc. 31 UV exposure and extremity flexion increase the potential for zinc 31 and titanium nanoparticles to be absorbed through intact skin. There is a concern about inhaling nanoparticles in Highly effective immunization can be achieved with nanoparticles. 32 The HPV vaccine is a nanoparticle vaccine which uses virus-like particles (VLP). 2 Inoculation directly into the lymph node with nanoparticles can produce a robust immune response. 33 The prediction of a 50-80% effectiveness for a COVID vaccine was fortunately an underestimation. Biotechnology to develop COVID-19 vaccines is superior due to the rapidity of development, cost-effectiveness, increased safety, and ease of manufacturing. 34 Most importantly, there is a highly effective ability to tune the vaccines in response to immune-evading, rapidly mutating viral variants. Emerging technology is not always successful, however. Effective vaccines for HIV and RSV have not been created, even with huge NIH investments. Herd immunity is predicted to develop when 70% of the world's population is immune (5.6 billion people). The Swedish experiment to allow natural infection to lead to herd immunity has proved disastrous. 8 This deadly pandemic be only be controlled and arrested with a safe and effective vaccine. 35, 36 Bioinformatics, cheminformatics, AI, Big Data, the Internet of Things, and machine learning can be useful in vaccine devel- Shapiro COVID-19 vaccines and nanomedicine Updates from medicine those epidemics was nonetheless crucial to the rapid development of COVID-19 vaccines. 45 One mRNA vaccine for COVID-19 was in clinical trials 66 days after the virus was sequenced. Adenovirus-based vaccines are being utilized. 46 67 Then we may finally be able to say we cured the common cold (those caused by coronavirus). Although it was certainly easier to go to the moon and Mars. What can we expect from first-generation COVID-19 vaccines? 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