7. Safety evaluation issues
Safety is a major concern of vaccines which needs due consideration while development, otherwise, failure of approval by a regulating agency is a certified outcome of the process. The formalin and UV-inactivated SARS vaccine and γ-radiation inactivated MERS vaccine developed a peculiar eosinophil-related lung pathology in mice following challenge. But when toll-like receptor agonists were associated with SARS vaccine there was reduction in lung pathology (Roper and Rehm, 2009; Schindewolf and Menachery, 2019). Another study with ferrets reported liver pathology following vaccination with modified vaccinia ankara (MVA) expressing S protein, however, no other studies supported such claims till date (Roper and Rehm, 2009). For COVID-19 vaccine development process S protein is the most targeted candidate antigen. Its biological characteristics, other than receptor binding and membrane fusion, are obscure (Zhang et al., 2020) which may potentially exert other biological activities affecting the vaccine safety and efficacy. On the other hand, ADE is a long-term obstacle in the development of vaccines against CoVs. This ADE has been observed with full-length S protein and is considered to be associated with the production of S protein specific antibodies (Wang et al., 2016; Liu et al., 2019). In hamsters SARS S protein based vaccine demonstrated ADE post-challenge but no such effect was observed in mice with S protein nanoparticle MERS vaccine following challenge dose (Roper and Rehm, 2009; Schindewolf and Menachery, 2019). However, it not clear yet which particular domain and which key amino acids in S protein of SARS-CoV are involved in the above safety issues with S protein vaccines. Therefore, a more basic research need to be carried out on the structure and function of this protein and mutations can be introduced at places in this protein to do away with such adverse effects (Zhang et al., 2020). The deficiencies and inconsistencies in the results pertaining to lung pathology, liver damage, and ADE observed in CoV infections among animal models necessitates an improved understanding of the biological basis for their occurrence and a better knowledge of human immunology to avoid similar reactions in humans.