Yu et al: 'mRNA vaccine-induced antibodies more effective than natural immunity in neutralizing SARS-CoV-2 & its high affinity variants'; conclusion is wrong, its not quantity that's key, its QUALITY
by Paul Alexander
Reported their data indicating that mRNA vaccination may generate more neutralizing RBD antibodies than natural immunity; potential need to maintain high RBD antibody levels; I say WRONG!
“Our data showed that N501Y RBD had fivefold higher ACE2 binding than the original variant. While some antisera from naturally infected subjects had substantially reduced neutralization ability against N501Y RBD, all blood samples from vaccinated individuals were highly effective in neutralizing it. Thus, our data indicates that mRNA vaccination may generate more neutralizing RBD antibodies than natural immunity. It further suggests a potential need to maintain high RBD antibody levels to control the more infectious SARS-CoV-2 variants.”
My input and I am disciple of Geert Vanden Bossche:
We know that naturally induced antibodies can neutralize a broader range of viral variants relative to mRNA-induced antibodies, which is potentially due to their higher level of learning (training) and thus affinity to the antigen (https://www.science.org/doi/pdf/10.1126/science.abg9175).
GVB argues that the level of COVID virus infectiousness is associated and linked with the strength of binding of the receptor binding domain (RBD) to cell-surface ACE-2 receptor, and an enhanced level of COVID virus infectiousness facilitates ACE-2 in outcompeting neutralizing antibodies that bind in high concentration to RBD. Geert argues that para “elevated resistance enables ACE-2 to outcompete neutralizing Abs that bind with high affinity to RBD’. The key conclusion and I strongly agree and why the findings above are sub-optimal and flawed is that it is not the quantity of of neutralizing antibodies, but rather the quality, also known as their affinity to the antigen. This will underpin the host’s immune system ability to resist the immune-evading viral mutations.
The problem is the binding affinity of mRNA vaccine induced Abs versus naturally induced Abs was not studied or tested here and this is the key.
Geert VB para “Since mRNA-induced Abs have lower affinity than naturally induced Abs, they are also more likely to exert suboptimal immune pressure on the infectiousness of viral variants that escape from virus-neutralizing Abs. In addition, the mRNA vaccine-induced Abs declined much faster than the naturally induced Abs.”
I firmly agree.
Importantly, ‘persons with strong innate immunity develop asymptomatic or mild infection and may not generate any neutralizing Abs at all (https://www.nature.com/articles/s41591-020-0965-6; https://www.nejm.org/doi/full/10.1056/nejmc2025179; https://pubmed.ncbi.nlm.nih.gov/32805631/); and those who do will develop high titers of neutralizing Abs upon re-exposure. Consequently, the study should not have used convalescent antisera but sera from naturally boosted subjects as a comparator.’
I cannot express how much I have learnt from Geert and he stands apart from all.