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.