New study tests how mutations in SARS-CoV-2 affect antibody neutralization

Using pseudoviruses with single amino acid substitution, researchers found that mutations in severe respiratory coronavirus 2 syndrome (SARS-CoV-2) reduced monoclonal antibody neutralization differently. However, convalescent sera samples did not lose much neutralizing strength and were also effective against B.1.1.7 weights (derived from the UK).

As SARS-CoV-2 continues to infect humans worldwide, it is also circulating. The majority of mutations are on virus spike proteins, the main viral component that binds to host cells and the main antigenic target for vaccines and antivirals. Because many vaccines, and antibodies from a previous infection, are based on the earlier circulating strains, it is not known how immunity affects the new strains.

One way to look for potential escape mutations is to look at sites with amino acid differentiation and compare them to the virus closest to SARS-CoV-2. , the acute respiratory coronavirus syndrome (SARS-CoV) – the pathogen responsible for SARS disease in China from 2002-4. Although both have different disease dynamics and outcomes, they target the human angiotensin converting enzyme 2 (ACE2) for viral entry and share about 75% of the amino acids in the protein spike.

New mutations of SARS-CoV-2 have been reported from the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1). They all have mutations in the spike protein binding (RBD) domain. The mutations in the South African and Brazilian strains are believed to reduce the strength of conventional vaccines to neutralize the virus.

In a new study published in Cell reports, researchers report the results of their study of how individual virus amino acid substitutes can help the virus escape antibodies.

Amino acid substitution affects antibody neutralization

Of the 56 amino acid differences between the RBD of SARS-CoV and SARS-CoV-2, the researchers looked at 15 that had amino acid substitution with a significant change in the biochemical character of the amino acid. as well as changes that occurred in order. occupations. They observed these positions on SARS-CoV-2 spike proteins to be equivalent to those of SARS-CoV and produced 12 pseudoviruses. They tested the neutralizing effect of monoclonal antibodies that came after SARS-CoV-2 infection. These antibodies were classified into different groups based on the target regions.

Three of the 12 pseudoviruses had no effect on the neutralization activity of the antibodies tested. The team identified seven mutations of the spike protein that reduced the neutralizing effect of at least one antibody. The worst effect was observed in the triple substitution of TEI470-2NVP, which reduced the potency of almost all monoclonal antibodies.

The neutralization effect is not based solely on where the antibodies bind, as antibodies that bind to the same area have different effects depending on the amino acid substitution.

The team tested the effect of serum neutralization collected from recovered patients on these mutations and found that the decrease in their potency was lower than the individual monoclonal antibodies. Sera collected from patients with true COVID-19 lost less neutralizing power compared to sera from patients with mild disease. This may be due to increased polyclonality from the increased antigenic stimulation during severe disease.

A virus can keep going

Although the researchers studied several amino acid substitutions, none of these were frequently seen in the circulating SARS-CoV-2 sequences. Therefore, they contributed to the mutations caused by the B.1.1.7 variant in their experiments. They found that, from the mutations, the N501Y significantly reduced the neutralizing strength of monoclonal antibodies, but although the conformation had less effect on the neutralizing strength of convalescent sera. All sera samples neutralized the B.1.1.7 variant, and only about 10% of the sera samples lost the neutralization potential.

This suggests that the different antibodies in the serum target the virus in different ways, making them as sensitive to spike mutations. However, studies have shown that the species B.1.351 (or of South African origin) resists nesting with a large fraction of convalescent sera. It is possible that a combination of mutations could lead to a greater neutralization effect than a single amino acid substitution.

Therefore, the findings suggest that most vaccines should be effective against B.1.1.7 strain, as the serum used in the trials was obtained in early 2020, and the circulating virus weight then is similar to those in the vaccines.

The study only analyzed RBD mutations, but other areas of susceptibility include N-terminal domains, which should be examined again. As the seropositivity of the population increases either due to natural or immunosuppressive infection, there may be a preference for spike mutations leading to large mutations and antigenic movement, which require continuous examination and ‘could affect the effectiveness of vaccines.