SARS-CoV-2 viral strain mutated quickly to evade antibodies and T lymphocytes in the plasma of a recovering patient. These changes are extremely rapid and worrisome in many ways.
A team of researchers has just highlighted the virus’s incredible ability to mutate to evade antibodies. The researchers, led by Rino Rappuoli (head of External R&D at GSK Vaccines), injected the original SARS-CoV-2 coronavirus strain into the plasma of a convalescent patient to see how the virus responded. For 38 days, the plasma neutralized the virus without a problem, even at 640-fold dilution. But it didn’t take long for the balance of power to reverse.
Three Mutations Were Enough to Overcome the Antibodies
At 45 days, the first mutation in the spike protein occurred in 36% of the virions and eluded the antibodies. Another passage later, the mutation affected 100% of the virions and had already reduced the plasma effect by four. After 12 passages and 80 days, the E484K mutation appeared. This is the same mutation that is present in the South African, Brazilian, and English variants. At that time, the resistance capacity of the serum was reduced again by four which made it 16 times less effective than at the beginning. A third change was observed after a final passage between days 80 and 90 (when the experiment was stopped) accompanied by “the complete abolition of neutralizing activity by the plasma sample,” noted the authors.
The final mutation, the spontaneous insertion of a long 11-amino acid chain at position 248 of the spike protein, is particularly interesting because it is a known immunogenic escape strategy that has been described in influenza, HIV-1, and other viruses. While this type of large-scale mutation usually takes years to emerge, here it happened in less than three months!
Why this Is a Problem
According to another recent study published in Science Immunology, some mutant peptides of the virus do not bind effectively to proteins on the surface of infected cells. This means that these cells cannot be recognized by CD8+ T cells, which are responsible for killing them. “These mutant peptides decrease T-cell proliferation, delay the production of inflammatory factors such as IFN-γ, and interfere with overall killer T-cell killing activity,” report the study authors, who examined 747 gene sequences of the virus to identify these key mutations
This news is all the more troubling because immunologists previously believed that T-lymphocyte action could compensate for reduced antibody efficacy. Moreover, some vaccines, such as RNA vaccines, induce a response against a limited number of epitopes recognized by CD8+ cells. This means that a few mutations in the virus could be enough to weaken their effectiveness.
Doctors treating patients with severe forms of COVID-19 should exercise caution when using convalescent plasma. Using convalescent plasma haphazardly could lead to more mutations that could render all the current vaccines obsolete.