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.