antibody-dependent enhancement (ADE) of CoV infection in
hyperimmune globulin therapy and vaccine
Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development
While development of both hyperimmune globulin therapy and vaccine against
SARS-CoV-2 are promising, they both pose a common theoretical safety concern . Experimental studies have suggested the possibility of immune-enhanced disease of SARS-CoV and MERS-CoV infections, which may thus similarly occur with SARS-CoV-2 infection (as discussed below).
The concern with antibody-dependent enhancement (ADE) of CoV infection arose from observations with feline infectious peritonitis virus (FIPV). FIPV infects myeloid-derived cells, such as macrophages, in cats . As the target cell of FIPV also expresses fragment crystallizable (Fc) receptors, antibody decorated FIPV could activate Fc receptors for entry into macrophages. Indeed, vaccines that produce low titers of neutralizing antibodies elicited more severe peritonitis and higher mortality rates in vaccinated kittens . Concerns were also raised on the possibility of ADE for SARS-CoV and MERS-CoV infections .
2.2. The Science
ADE of infection can be elicited in vitro for many different viruses, including human immunodeficiency virus [15,16], influenza  and Ebola viruses [18,19]. Similarly, in vitro ADE of wild-type virus and pseudotype viruses into Fc receptor-expressing myeloid-derived cells in the presence of sub-neutralizing concentrations of immune sera has also been described for both SARS-CoV and MERS-CoV [14,, , ]. For CoVs, it has been shown that antibodies can bind the surface spike protein exposing the virus to proteolytic activation and Fc receptor-mediated entry . However, in vitro observations need to be interpreted with caution, since few diseases have been clinically associated with ADE. The most prominent disease associated with ADE is arguably dengue, where infection with one serotype of dengue virus (DENV) predisposes a person to a more severe disease upon secondary infection with a heterologous DENV serotype [23,24]. A similar phenomenon was responsible for increased hospitalization rates following vaccination of dengue-naïve individuals with the chimeric tetravalent yellow fever-dengue vaccine, Dengvaxia® . Besides dengue, several other viruses have shown clinical or epidemiological evidence to support the notion of ADE. Two notable examples of vaccine-induced ADE are respiratory syncytial virus (RSV) , , ,  and atypical measles [30,31], where severe disease was more prevalent following vaccination with inactivated virions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161485/#bib0011