5.3. Route of administration and regimen
Indicating the most operative application route and suitable regimen is
the third pillar of an effective vaccination [44]. These are more
prominent for mucosal infectious agents like the current SARS-CoV2 and
those pathogens that require priming innate as well as cellular and
antibody immune responses for full protection [45]. The best period
to control and clear SARS-CoV2 infection is within the first 2 to 12
days after infection, when the person has no clinical symptoms and
essential immune components should be placed in the lung mucosa before
the viral entry [9]. In this regard, one of the effective variables
is the route of vaccination [44]. For instance, intramuscular
injection of influenza or measles vaccines mainly induce protective IgG
responses that willingly appear in respiratory mucosa, but had no
considerable effects on lung mucosal immunity, including the specific
IgA secretion and stimulation of tissue resident memory T cells
[46]. Conversely, respiratory mucosal vaccination led to acceptable
mucosal antibody responses, priming lung resident memory T cell and
inducing trained immunity in macrophages [47, 48]. The pulmonary
administration is not a preferred route for the killed, nucleic acid and
subunit vaccines since the use of potential adjuvants and re-boost doses
is inevitable for such platforms [8]. In contrast, viral
vector-based vaccines specially those applying adenovirus vectors like
serotype 5 of human adenovirus or adenovirus obtained from a chimpanzee
host are suitable candidates for respiratory mucosal vaccination
[49]. However, most common human vaccines as well as low immunogenic
viral vectors such as adenovirus serotype 26 requires repeated similar
administration for effective primed immunity. It is not yet clear which
vaccination strategy is to be used to combat COVID-19 pandemic and how
long this strategy will last in recipient bodies, but it may be
necessary to use the same or different vaccination regimen for repeated
injections in order to reinforcing protection, such as
chimpanzee-derived adenovirus (ChAd) [8]. The route of
administration may also change in subsequent repeated vaccinations.
6. Stages of vaccine
advancement
Unveiling of a new vaccine product contain strict Research and
Development (R&D) procedures that the manufacturer should be fully
committed to implementing it before obtaining a marketing license
[27]. Also, the United States Food and Drug Administration (U S
FDA), WHO, European Medicines Agency (EMA) and the national authorities
have enacted scrupulous regulations regarding the accurate clinical
evaluation of vaccine development [50, 51]. The reason for such
strict regulations in the development of a new vaccine compared to other
drug compounds is the potential for mass and global production and
prescription for a wide range of healthy people, including pregnant
women, elderly and the young population. Briefly, clinical trial testing
of vaccine products is generally divided into four step-by-step phases
including Exploratory trials, Preclinical, Clinical, and Post-marketing
stages that will normally proceed over many years. Also, the clinical
trial study containing three consecutive stages (I, II and III) that the
legal permissions including “Clinical Trial Authorization” before the
phase I to enter human experiments and the “Biological License
Application Approvals” for vaccine marketing after the completion of
phase III are required respectively (Table 1) [51].
Table 1. Major characteristics of vaccine development processes