“[E]xtreme caution must be taken to scrutinize backfire-effects i.e. the undesirable adverse effects (Table 2). One such dangerous backfire is vaccine-induced enhancement, which has been a major bottleneck in the development of certain corona-, flavi-, lenti-, and paramyxovirus vaccines. Here, antibody-dependent enhancement (ADE) performs a key role (Huisman et al., 2009). One study reported that the recombinant vaccinia virus Ankara expressing the S protein of SARS-CoV increased hepatitis in ferrets (Weingartl et al., 2004). Anti-S protein IgG against SARS-CoV caused severe acute lung injury in macaques (Liu et al., 2019). New Zealand white rabbits displayed increased lung inflammation after re-infection with MERS-CoV due to the lack of non-neutralizing antibodies and complement proteins (Houser et al., 2017). Researchers assume that SARS-CoV-2 severity is a consequence of ADE (Tetro, 2020). However, a study opined that the ADE and immunopathology are linked to the inflammatory feedback of host Th17, and this can be overcome by using alum as an adjuvant (Hotez et al., 2020). Now, the question arises. Will it be possible to overcome the backfires in developing COVID-19 vaccine? In brief, researchers need to resolve these questions to develop effective and safe vaccines against COVID-19 infection.”
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