14. Conclusion and future guideline
The world is still battling the novel SARS-CoV2 virus, and to date, various companies and research institutes have offered several treatment strategies to combat the pandemic. Given the experience of parallel coronavirus epidemics during the past decades, the only solution seems to obtain a safe and effective vaccine against COVID-19. Tireless efforts have led to the development of 242 COVID-19 vaccines candidates, of which 20 have entered the phase III large-scale efficacy human trials. Although we are still in the early stages of SARS-CoV2 identification and vaccine preparation, multiple similar vaccines especially based on advanced platforms have been extensively studied for other infectious diseases and cancers. Therefore, applying the existing knowledges available in similar researches can guide us in using the best vaccination strategy and platform. Most current researches on COVID-19 vaccine candidates have focused on intramuscular or skin administration. Based on the initial findings of the present studies and considering similar previous researches, it can be inferred that COVID-19 parenteral vaccines are most likely provide protection through the induction of durable neutralizing antibodies and acceptable T cell responses. On the other hand, SARS-CoV2 is mainly transmitted through respiratory ducts and causes annoying pulmonary symptoms, so paying attention to respiratory mucosal vaccination strategies, especially in high-risk people, may lead to the initial control and clearance of the SARS-CoV2. Moreover, this mucosal vaccination strategy is needle-free and desponds on a lower dose of antigen than parenteral vaccines. However, not all vaccine platforms are safe and effective for respiratory mucosal vaccination, and providing broad-spectrum inhaler vehicles for mucosal vaccine delivery is one of the crucial limitations. As mentioned, the use of vaccine platforms that depends primarily on adjuvants to strongly stimulate especially T cell responses are costly and not suitable for respiratory mucosal administration. On the other hand, attenuated live vaccines are not recommended, especially for highly mutable viruses such as SARS-CoV2, due to the increased risk of pathogenic conversion. Viral vector vaccines are also potent stimulants of antibody and T cell responses, but sometimes their effectiveness is affected by pre-existing cross-reactive immunity. VLP-based vaccines are also the other potential candidates with established capacities in human studies. Although providing suitable VLP that covering all the expected characteristics is challenging. Nucleic acid vaccines also have a high chance of success against COVID-19, but there are obstacles such as lack of human safety data, need for specific delivery vehicle and depending on adjuvants. With this in mind, it seems that vaccines based on advanced platforms such as VLP, viral vector and nucleic acid vaccines have a higher chance of success in the COVID-19 vaccine race. Given the current situation, the pattern of vaccine design and manufacturing has been greatly overstuffed and led to even preclinical and clinical evaluations running in parallel. Therefore, the provisional data from the initial analysis of vaccine studies are being available in real time, but it does not provide valuable information regarding the durability and quality of obtained protective immunity. In many countries, the transmission rate and the new cases of the COVID-19 disease is significantly declining, and it is unclear whether the results of operating clinical trials of pioneering vaccine candidates in such volunteer countries will be reliable. Also, the separate reported efficacy of some vaccine candidates in various areas makes it a bit difficult to compare them simultaneously, and it is still too early for goal celebration in achieving a suitable efficacy and safety for COVID-19 vaccine candidates. However, given the current critical situation, emergency application of vaccine candidates with approved preclinical potential and encouraging but limited clinical outcomes is the best solution, at least for endangered people. Inevitably, the evolving clinical trials will continue in the coming years until the longevity and quality of vaccine-induced immunity as well as the functionality of vaccination strategies be better understood. Therefore, until attaining a certain level of confidence in COVID-19 vaccine candidates, universal vaccination of all masses is unreasonable. It is noteworthy that, due to the existing challenges such as providing resources, formulating and distribution as well as ecumenical available different vaccine strategies and platforms, the implementation of the vaccination program will not be smooth and uniform. Hence, foundations such as COVID-19 Vaccines Global Access (COVAX) and the Coalition for Epidemic Preparedness Innovations (CEPI) have been set up to do their utmost to unite rich and low-income countries to achieve fair, transparent and rapid access to the most effective COVID-19 vaccine candidates globally.