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Bernard: "The Sinopharm and AZ vaccines have shown to be less efficient than the mRNA vaccines"

and there is a reason for that.

How SARS-CoV-2 first adapted in humans

The key is that both the RBD-up conformation and dissociation of S1 from S2--enabled by furin cleavage--require disordering of the 630 loop. Thus, the RBD-up conformation can be more easily accessed with the original D614 S protein, but once this conformation is achieved, this S protein is more likely to fall apart entirely owing to premature shedding of its S1 domain. Conversely, with G614, more energy is required to achieve a one RBD-up state, but dissociation of S1 from S2 also becomes less favorable because the remaining folded 630 loops continue to hold the trimer together. Thus, the D614G variants have more S proteins in the up orientation because the next, irreversible step toward inactivation is slower. Infection with D614G is more efficient because it prevents premature S1 shedding

These structural studies have real-life implications. All current vaccines are based on the original, unstable D614 form of the S protein. Fortunately, most vaccine developers, including Moderna and Pfizer-BioNTech, took a lesson from studies of SARS-CoV-1 and Middle East respiratory syndrome (MERS) coronavirus to slow S-protein shedding by introducing non-native prolines into S2. Those who developed the Johnson and Johnson and Novavax vaccines had the prescience to also remove the furin site. By contrast, the developers of the University of Oxford-AstraZeneca vaccine opted for the wild-type S protein (containing D614), as is also the case for the inactivated virus vaccine produced by Sinovac. To be clear, other variables, especially antigen-delivery systems, likely account for efficacy differences among these vaccines. However, apples-to-apples studies in animals make clear that both engineered prolines and furin-site ablation contribute to vaccine effectiveness. It is almost certain that the next round of vaccines, those better reflecting the S-protein variants now in circulation, will include D614G. Vaccines that express unmodified S proteins with G614 may enjoy a relative jump in potency because this change compensates for the lack of engineered stabilizing mutations.

[Emphasis added]

She believed in nothing; only her skepticism kept her from being an atheist. -- Jean-Paul Sartre

by ATinNM on Sun May 9th, 2021 at 03:04:20 PM EST
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