A comprehensive comparison between COVID-19 vaccines: a review

10 COVID-19 started in December 2019 in Wuhan and spread worldwide. The cause of COVID-19 11 is the newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS- 12 CoV-2). Until now, this pandemic is affecting almost every country in the world and over 100 13 million cases were confirmed. It is expected that vaccination could be a beneficial way to control 14 and protect against COVID-19. This review aimed to compare 4 platforms of COVID-19 15 vaccines and used recently developed vaccines candidates as examples to illustrate. Safety, 16 efficacy, scaling, cost, and adaptation to the mutated virus were included. Theoretical and 17 clinical vaccine research results were used and we attempted to conclude the advantage and 18 disadvantage of each candidate platform. Countries should choose an appropriate vaccine for 19 their people and satisfy the demand for vaccines.


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In late 2019, several cases of pneumonia of unknown cause was discovered in Wuhan, China, 23 and was reported to the World Health Organisation (WHO). In February 2020 the virus was 24 named SARS-CoV-2, and the pandemic is named COVID-19. (Simon, Nilianjan, Jyotismita 25 2020) Afterwards, a pandemic from the coronavirus has stormed the world. This disease has 26 spread worldwide, leading to go an ongoing pandemic(Zimmer, Carl 2021). To date, there are 27 over 100 million infections and over 2.5 million deaths. And the virus has been mutated into 28 about 30 strains of which there are more infectious and lethal ones. Prevention and treatment of 29 COVID-19 have been a challenging situation to all human beings. Against the pandemic, 30 humans have developed multiple methods, one of the most helpful one is the vaccination. 31 Vaccination allows people to acquire immunity against the virus and provides long-term 32 protection. Herd immunity could be achieved when large population have received vaccines 33 (Why is vaccination so important, 2021). Vaccine development of this pandemic is facing many 34 concerns. Means of manufacturing and transport must be adjusted for different countries and subunit vaccines, to novel platforms like mRNA vaccines, candidates from various platforms 44 have joined the vaccine race. Each route has its own advantages and disadvantages. This paper 45 aims to discuss and compare the routes of vaccine development, in order to provide reference for 46 the needed individuals and organizations.  Theoretically, there are several advantages of developing a mRNA vaccine. First, its deisgn and 74 production are rapid (Funk, Laferriè re and Ardakani, 2020), which would be particularly suitable 75 for the current situation given the severity of the pandemic. Second, unlike inactivated vaccines, 76 the development of a mRNA vaccine do not require the handling of infectious materials, which 77 would make the production safer (Funk, Laferriè re and Ardakani, 2020). Third, they are able to 78 induce a strong and quick antiviral response, both humoral and cell-mediated (Funk, Laferriè re 79 and Ardakani, 2020). Lastly, the scaling up for a worldwide production would be feasible (Funk,80 Laferriè re and Ardakani, 2020).

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However, development of mRNA vaccines are relatively immature compared to other 83 conventional ways of developing vaccines as there were no approved mRNA vaccines before 84 COVID-19. It also possible that inflammatory reactions may be induced (Funk, Laferriè re and 85 Ardakani, 2020). Besides, most formulations require a cold chain for storgae in order to sustain 86 the vaccines' longevity and stability, which could be quite inconvienent for developing countries 87 or regions. Moreover, boosting would likely be necessary to achieve long-lasting immunity 88 (Funk, Laferriè re and Ardakani, 2020), which again, may cause some inconvenience in the 89 developing world.  An inactivated vaccine is synthesised by inactivating or killing a pathogen, in hopes of 125 decreasing its infectivity without compromising its immunogenicity (Callaway, 2020). The 126 vaccine is administered in vivo with adjuvants (Callaway, 2020). Starting with a strain, the 127 viruses are exposed to either chemical or physical agents, such as formaldehyde or heat, to              The safety of vaccines varies among routes. All vaccines share some side effects, mild or severe,

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Inactivated vaccine has a relatively higher level of safety because they used killed pathogen and 328 they could not convert into a more threatening phenotype. According to phase 1/ 2 trial of 329 BBIBP-CorV, 29% of recipients had adverse events like fever, but are mild (Xia et al., 2021).   Furthermore, thoretically, infection and genomic integration into the host cell DNA would not be 348 a concern for mRNA vaccines (Pardi et al., 2018). However, a potential concern is that mRNA  All vaccines are effective and efficient in theory, but the human body is a complicated system, 361 all theories remain to be proven by real-world obseravation. The mRNA and adenovirus may 362 enter human cells for production of antigen, thus they stimulate both humoral and cellular 363 immunity, which is superior to the other two. But efficacy of adenovirus vaccine might be 364 affected by pre-existing immunity against adenovirus. And the immunity developed by subunit 365 vaccine could be easily escaped by mutated virus. As the body of human is a huge and 366 complicated system, all theories remain to be proven by real-world oberavation.

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Inactivated viruses have no replicability in vivo, and it has lower immunogenicity. Adjuvants are 369 used to compensate for this weakness (Ulmer, Valley and Rappuoli, 2006). The efficacy of the     Oxford-AstraZeneca has 4 manufacturers to produce their vaccine and the scale were all above 405 100 million doses per year (Majumder, 2021).

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mRNA vaccines are relatively easier to scale-up. This is because mRNA vaccines can be 408 synthesied in vitro without working with live viruses. The production of the vaccine was simple 409 and quick because it was cell-free, only an aqueous phase enzymatic reaction was involved 410 (Stanton, 2020). Productions for other platforms like inactivated vaccines, which involve cells, 411 require bioreactors that provide massive space for cell growth (Stanton, 2020). The large space is 412 essential as to lower competition for resources among cells within the same bioreactor.   In this paper, we have discussed, and compared aspects of vaccine routes, including the principle 513 and manufacturing, safety and efficacy, scaling and cost, etc. What we have found out is that the 514 inactivated vaccine might be less efficient, while it could be the safest one, and the need of 515 biosafety equipment makes it expensive and less scalable. Meanwhile, mRNA vaccines have 516 been demonstrated to be effective and safe, and mRNA's systhesis tends to be simple. However, 517 they require stringent storage and transportation conditions. Subunit vaccines are applicable to 518 people who have weak immune systems and safe to use, they can be produced in the 519 fermentation tank with mass production, but they have the worst resistance to mutation.

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Adenovirus vaccine has an efficacy between mRNA vaccine and subunit vaccine but is harder to 521 scale up. It is preferable for developing countries because the storage and transport condition is 522 more likely to be achieved. In summary, each route has its advantages and disadvantages.

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Authorities need to apply the route that fits the reality best. For a developed country, the mRNA 524 vaccine might be a good choice for its high efficacy. While for the developing countries, where 525 there are no enough freezers for transport and storage of vaccine, subunit vaccine outstands for 526 high safety and low price. COVID-19 is an unfortunate tragedy to the whole population. For the 527 sake of the safety and wellbeing of all humans, we urge pharmaceutical companies, universities, 528 governments and everyone, to put down our differences and battle our common enemy. With 529 concerted effort, we shall prevail.    16) Xia, S., Duan, K., Zhang, Y., Zhao, D., Zhang, H., Xie, Z., Li, X., Peng, C., Zhang, Y., 596 Zhang, W., Yang, Y., Chen, W., Gao, X., You, W., Wang, X., Wang, Z., Shi, Z., Wang, Y.,