4.4. Immunity period
It should be noted that in order to achieve a successful vaccination, the development of associated antibody and cellular immune responses against SARS-CoV2 should be sustained for a long time. The SARS-CoV2 spends a limited time in our communities, and it is too early to comment on the longevity of induced protective immune responses with high certainty. Although, it is possible to somewhat predict the quality and longevity of antibody and T cell responses to the COVID-19 vaccine candidates by inspiration from vaccine studies for two closely related coronaviruses, MERS and SARS , which have provided promising long-lasting protective immune responses [33, 34].
4.5. Disease enhancement phenomenon
The biggest challenge is that not only the designed vaccine award immunity against the desired infectious agent but also aggravates the course of the disease and enhanced mortality [34, 35]. disease enhancement or antibody-dependent enhancement (ADE) is such a wrecking process that mediated by non-neutralizing antibody responses against vaccine candidates. This phenomenon aborts the vaccine project by vitiating the elementary vaccination goal and making the disease worse. Indeed, the ADE is mediated by Fc receptor or complement coated cells that following antibody attachment, reverted immune responses from Th1 (interleukin (IL)-2, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ)) toward Th2 responses (IL-10, IL-6, prostaglandin (PGE2), IFN-α) and blocking signal transducer and activator of transcription (STAT) signaling pathways leading to unbridled viral replication [27]. So, regarding the ADE as the major bane of successful vaccination, maximum efforts should be done to identify efficient immunodominant epitopes and prevent the development of dysfunctional antibodies responsible for the disease exacerbation.