They are needed to confirm which populations remain at greatest risk when vaccines become available and to establish a globally fair vaccine distribution system (Lurie et al., 2020). As described by Funk et al. a combination of different vaccines may boost logistics and immunization. trials is an emerging and innovative field that can be applied to predict and simulate immune, molecular, clinical, and epidemiological outcomes of vaccines to refine, reduce, and partially replace steps in vaccine development. Vaccine-resistant variants of SARS-CoV-2 might emerge, leading to the necessity of updates. A globally fair vaccine distribution system must prevail over vaccine nationalism for the world to return to its pre-pandemic status. Keywords: SARS-CoV-2, Coronavirus, Vaccine strategies, Vaccine safety, Emergency use 1.?Vaccine development attempts for previous coronaviruses The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly. Coronavirus disease 2019 (COVID-19) has been the cause of millions of deaths and social and economic crises worldwide. The scientific community has been exploring all SRT 2183 strategies to develop efficient vaccines against SARS-CoV-2, which is essential to reduce morbidity and mortality (Hodgson et al., 2020). Social distancing strategies help prevent transmission and reduce infection, but a vaccine is necessary for the population to acquire immunity against COVID-19. Attempts to develop several vaccines for -coronaviruses, closely related to SARS-CoV-2, such as SARS-CoV and MERS-CoV, were previously performed and tested in animal models (Roper and Rehm, 2009). Most vaccines protected animals from a challenge with SARS-CoV or MERS-CoV although many of them did not induce long-term immunity. In addition, vaccination resulted in SRT 2183 complications in some cases, including lung damage and infiltration of eosinophils in a mouse model (Bolles et al., 2011; Agrawal et al., 2016). About 40C60 % of unexposed healthy individuals from the United States (n?=?20) presented SARS-CoV-2-reactive CD4?+?T cells, indicating the presence of a cross-reactivity immunity for other common coronaviruses (Grifoni et al., 2020). Efforts for SRT 2183 vaccine development for SARS-CoV and MERS-CoV were made but failed, so the immune system managed to spontaneously suppress the infection in the population. Although their candidate vaccines have been submitted and are still in progress, there are SRT 2183 no approved vaccines for these infectious agents so far, after 17 and 6 years of the original outbreaks, respectively (De Wit et al., 2016; Song et al., 2019). Therefore, the highest scientific standards are required for the effective development of a vaccine against COVID-19. Although previous experiments for SARS-CoV and MERS-CoV indicated potential harmful and adverse events due to increased immunity (Prompetchara et al., 2020), it is possible to learn from those vaccine attempts for other coronaviruses about how to move forward with a SARS-CoV-2 vaccine project. 2.?Vaccine development for COVID-19 in a pandemic paradigm A vaccine should produce specific and neutralizing SRT 2183 antibodies. The goal is to expose the body to an antigen that stimulates the immune response, blocking or eliminating the virus in case of infection, without triggering COVID-19. Vaccines may cause adverse events that are harmful to the host due to unwanted immune enhancement responses, so careful and complete tests are required before the approval of a global vaccine for COVID-19 (Funk et al., 2020). Designing a vaccine requires a selection of antigens and platforms as well as forms of administration and regimen. While only antibodies to the spike (S) protein can neutralize and prevent infection, the inclusion of the nucleocapsid (N) or a non-structural protein as antigen can probably produce a balanced humoral and T-cell immunity. The route of administration and regimen significantly depends PBX1 on the vaccine strategy. However, parenteral vaccination is regarded to induce timely IgG antibodies while the respiratory route better induces resident memory T cells (TRM) and trained immunity in the lungs (Jeyanathan et al., 2020). Scientists believe that COVID-19 severe symptoms may be better explained by the immunopathology of the Th2 response (Roncati et al., 2020). This immunopathology is based on the unregulated response of T cells, with an increased response of CD4?+?T cells specific to the virus, leading to allergic inflammation and an influx of eosinophils into the lungs (Tseng et al., 2012). studies have shown that infection by SARS-CoV after vaccination failed to control viral replication, increase of clinical symptoms, and pathology characterized by distorted Th2 responses, inflammation, and eosinophilic influx (Bolles et al., 2011; Tseng et al., 2012). It was also observed that pathological development might be linked to antibodies specifically targeted to the nucleocapsid protein (Bolles et al., 2011). However, a reduction in pathology was observed in vaccination studies with the spike protein (Tseng et al.,.