SARS-CoV-2 spike E484K mutation reduces antibody neutralization

Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, the coronavirus disease 2019 (COVID-19) pandemic continues to wreak havoc globally. Meanwhile, scientists race to develop therapeutics and vaccines to mitigate its severity and control its spread.

However, faster spreading and potentially more fatal SARS-CoV-2 variants have undermined efforts to turn the tide of the pandemic. Researchers at the Department of Microbiology, Icahn School of Medicine at Mount Sinai New York, USA, showed that the SARS-CoV-2 spike E484K mutation reduces antibody neutralization. Their findings have been published in The Lancet.

Study: SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. Image Credit: joshimerbin / Shutterstock
Study: SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. Image Credit: joshimerbin / Shutterstock

Study background

More than a year into the COVID-19 pandemic, the virus continues to spread, with new variants emerging. To date, three variants are of particular concern:  the B.1.1.7 or the United Kingdom variant, the B.1.351 or the South African variant, and the P.1 or the Brazilian variant.

Previous reports showed that emerging SARS-CoV-2 variants could evade neutralizing antibodies induced by previous infection or vaccination through mutations in the spike protein. This includes the receptor-binding domain (RBD).

The well-known asparagine (N) to tyrosine (Y) substitution at position 501 (N501Y), which is present in variants B.1.1.7, B.1.351, and P.1, does not seem to impact in vitro neutralization of human convalescent or post-vaccination sera.

However, like the E484K found in B.1.351 and P.1 lineages, additional substitutions allow evasion from neutralizing antibodies. This means that people who had the infection and vaccines may still get infected with these variants.

The study

To arrive at the study findings, which were published in the journal The Lancet, the researchers conducted in vitro microneutralization assays with the USA-WA1/2020 virus and a recombinant (r) SARS-CoV-2 virus, which is similar to USA-WA1/2020 except for the E484K mutation introduced in the spike receptor-binding domain (RBD).

Overall, the team collected 34 sera from the study participants based on their SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) antibody titer. Further, they added the sera from five vaccinated people with the Pfizer-BioNTech COVID-19 vaccine or the BNT162b2 vaccine.

The study findings showed that the SARS-CoV-2 virus with E484K had lower serum neutralization efficiency than the USA-WA1/2020 for vaccinated and convalescent samples.

This means that the single E484K mutation in the RBD impacts the binding of serum polyclonal neutralizing antibodies. A loss of neutralization of the E484K recombinant virus may result from the decreased neutralization efficiency for sera with low or moderate levels of immunoglobulin G (IgG) against the SARS-CoV-2 spike protein.

The single mutation, the E484k, in lineages B.1.351 and P.1, affects the neutralizing activity in convalescent sera, which were from those who were infected with SARS-CoV-2 and post-vaccination sera.

Meanwhile, sera containing high neutralization titers against the USA-WA1/2020 strain still neutralized E484K rSARS-CoV-2. Hence, vaccinations should stimulate the highest neutralization titers possible to make the most of the protection against the evading strains of the virus.

Most COVID-19 vaccines are considered prime-boost regimens. Due to vaccine shortage, some countries recommended postponing the booster vaccination to protect more people. Yet, this will lead to having lower neutralizing antibody titers.

Our data suggest that lower neutralizing antibody titers might be problematic in the context of newly emerging SARS-CoV-2 variants, considering that this approach could leave some vaccinees unprotected,” the team noted.

The team also recommended that worldwide vaccination efforts should focus on fully vaccinating as many people as possible. To do this, public health officials should consider using vaccination strategies to induced high neutralizing antibody titers.

To date, over 135.74 million cases of COVID-19 have been reported. Of these, 2.93 million have died. The United States reports 31.18 million infections and over 561,000 deaths.

Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.

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