Moderna and Pfizer vaccines neutralise variants encoding mutations E484K or N501Y but with less potency

In a small cohort involving just 20 trial participants, researchers have found that both Moderna and Pfizer-BioNTech are able to neutralise SARS-CoV-2 variants encoding mutations E484K or N501Y or the K417N:E484K:N501Y combination.

However, the neutralizing activity decreased one to three-fold in the case of the variants with E484K or N501Y or a combination of mutations. Results were published in the journal Nature.

Both Moderna and Pfizer-BioNTech vaccines showed no significant difference in neutralising activity. Individuals immunized with either Moderna or Pfizer-BioNTech vaccines produce closely related and nearly identical antibodies.

Plasma neutralizing activity of volunteer plasmas was determined using human immunodeficiency virus-1 (HIV-1) pseudotyped with SARS-CoV-2 Spike protein. Vaccine plasma was significantly less effective in neutralizing the pseudotyped virus with certain mutations of the S proteins.

To examine the neutralising breadth of the monoclonal antibodies the researchers from the Rockefeller University, New York tested 17 of the most potent antibodies. They found that neutralisation by 14 of the 17 most potent antibodies was reduced or abolished by either K417N, or E484K, or N501Y mutations.

E484K is an escape mutation because it helps the virus slip past the body’s immune defences. The E484K mutation was first identified in the South African variant (B.1.351). The E484K mutation is also found in the Brazilian variant (B.1.1.28). The E484K mutation has also been in the U.K variant (B1.1.7).

The mutant N501Y has been found in both the UK and South African variants.

The researchers say that as seen in natural infection, a majority of the antibodies tested (9/17) were at least ten-fold less effective against pseudotyped viruses carrying the E484K mutation. While five of the antibodies were less potent against K417N, four were less potent against N501Y by ten-fold or more.

“We conclude that the plasma neutralizing activity elicited by either mRNA vaccination or natural infection is variably but significantly less effective against pseudoviruses that carry RBD mutations found in emerging SARS-CoV-2 variants,” the researchers write. “The mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.”

The results show why vaccination elicited better antibody response compared with naturally infected people. They found the IgG and IgM levels were significantly higher in the vaccinated group compared to a cohort of convalescent patients assayed 1.3 and 6.2 months after infection.

However, in the case of IgA, the levels were similar in both vaccinated and naturally infected people. “There was a broad range of plasma neutralising activity 3-14 weeks after the second vaccine dose that was similar to that elicited by natural infection in a convalescent cohort after 1.3 months, and greater than the activity at 6.2 months after infection,” they write.

The vaccines elicit antibody responses against the RBD, the major target of neutralizing antibodies, much like a natural infection. “Notably, the neutralizing antibodies produced by mRNA vaccination target the same epitopes as natural infection,” they note.