IROM
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- Feb 25, 2020
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From 1-3 it looks like they did a lot wrong. It wasn't broad spectrum, it didn't induce protection against infection and it included FULL LENGTH S-PROTEIN which is a major vehicle for Antibody Dependent Enhancement (ADE).
Author affiliations: *New York Blood Center, New York, New York, USA
Volume 11, Number 7—July 2005
SARS Vaccine Development
Shibo Jiang* , Yuxian He*, and Shuwen Liu*Author affiliations: *New York Blood Center, New York, New York, USA
My note on this is that the Pfizer and Moderna vaccines both have FULL S PROTEIN antibody reliance instead of the recommended truncated S PROTEIN....Polyclonal and monoclonal antibodies against S protein of the late SARS-CoV (Urbani strain) could neutralize infection by the relevant late SARS-CoV strains. However, these antibodies enhanced infection by an early human SARS-CoV isolate (GD03T0013) and the civet SARS-CoV–like viruses. These investigators have shown that the ACE2-binding domain mediates the antibody-dependent enhancement of civet SARS-CoV–like virus entry (6). Theoretically, some antibodies to the ACE2-binding domain may enhance infection if these antibodies closely mimic the receptor ACE2 and induce similar conformational changes, as the receptor likely does. The S protein with truncation at aa 1153 failed to cause antibody-dependent enhancement of infection, although it still induced neutralizing antibodies. This finding suggests that removal of the aa 1153–1194 region may abrogate induction of virus infection–enhancing antibodies
Conclusions
An ideal SARS vaccine should 1) elicit highly potent neutralizing antibody responses against a broad spectrum of viral strains; 2) induce protection against infection and transmission; and 3) be safe by not inducing any infection-enhancing antibodies or harmful immune or inflammatory responses. Currently, an inactivated SARS-CoV vaccine is in clinical trials in China. Safety is the major concern for this type of vaccine (12). The S protein is the major inducer of neutralizing antibodies. Recombinant vector-based vaccines expressing full-length S protein of the late SARS-CoV are under development. These vaccines can induce potent neutralizing and protective responses in immunized animals but may induce antibodies that enhance infection by early human SARS-CoV and animal SARS-CoV–like viruses (6). Recent studies have demonstrated that recombinant RBD consists of multiple conformational neutralizing epitopes that induce highly potent neutralizing antibodies against SARS-CoV (9,26,35–38). Unlike full-length S protein, RBD does not contain immunodominant sites that induce nonneutralizing antibodies. RBD sequences are relatively conserved. Thus, recombinant RBD or vectors encoding RBD may be used as safe and efficacious vaccines for preventing infection by SARS-CoV with distinct genotypes.