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